22 results on '"Ben Aissa, Assma"'
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2. Rapid diurnal variation of serous retinal detachment during BRAF and MEK inhibitor treatment: A case series.
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Bravetti, Giorgio Enrico, Muggler, Kevin, Ben Aissa, Assma, Thumann, Gabriele, and Malclès, Ariane
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RETINAL detachment ,BRAF genes ,PROLIFERATIVE vitreoretinopathy ,ACUTE kidney failure ,UVEA cancer ,MITOGEN-activated protein kinases - Abstract
This article presents two case studies of patients with metastatic melanoma who experienced daily fluctuations of serous retinal detachment (SRD) while being treated with a combination of encorafenib and binimetinib. The patients reported acute blurred vision that worsened in the morning and resolved by noon. Ophthalmologic examinations and scans revealed an increase in SRD between 8 and 11 AM, followed by complete resolution by 12 PM. The fluctuations persisted throughout the day and were observed during follow-up visits. Despite the subjective complaints, the treatment was not discontinued due to preserved visual acuity and the medications being the last-line therapy for metastatic melanoma. The authors suggest that the timing and dosage of the medication may be correlated with the rapid fluctuation of SRD, and emphasize the importance of appropriate follow-up for patients undergoing this therapy. [Extracted from the article]
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- 2024
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- View/download PDF
3. The T cell differentiation landscape is shaped by tumour mutations in lung cancer
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Ghorani, Ehsan, Reading, James L., Henry, Jake Y., Massy, Marc Robert de, Rosenthal, Rachel, Turati, Virginia, Joshi, Kroopa, Furness, Andrew J. S., Ben Aissa, Assma, Saini, Sunil Kumar, Ramskov, Sofie, Georgiou, Andrew, Sunderland, Mariana Werner, Wong, Yien Ning Sophia, Mucha, Maria Vila De, Day, William, Galvez-Cancino, Felipe, Becker, Pablo D., Uddin, Imran, Oakes, Theres, Ismail, Mazlina, Ronel, Tahel, Woolston, Annemarie, Jamal-Hanjani, Mariam, Veeriah, Selvaraju, Birkbak, Nicolai J., Wilson, Gareth A., Litchfield, Kevin, Conde, Lucia, Guerra-Assunção, José Afonso, Blighe, Kevin, Biswas, Dhruva, Salgado, Roberto, Lund, Tom, Bakir, Maise Al, Moore, David A., Hiley, Crispin T., Loi, Sherene, Sun, Yuxin, Yuan, Yinyin, AbdulJabbar, Khalid, Turajilic, Samra, Herrero, Javier, Enver, Tariq, Hadrup, Sine R., Hackshaw, Allan, Peggs, Karl S., McGranahan, Nicholas, Chain, Benny, Swanton, Charles, and Quezada, Sergio A.
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- 2020
- Full Text
- View/download PDF
4. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution
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Abbosh, Christopher, Birkbak, Nicolai J., Wilson, Gareth A., Jamal-Hanjani, Mariam, Constantin, Tudor, Salari, Raheleh, Le Quesne, John, Moore, David A., Veeriah, Selvaraju, Rosenthal, Rachel, Marafioti, Teresa, Kirkizlar, Eser, Watkins, Thomas B. K., McGranahan, Nicholas, Ward, Sophia, Martinson, Luke, Riley, Joan, Fraioli, Francesco, Al Bakir, Maise, Grnroos, Eva, Zambrana, Francisco, Endozo, Raymondo, Bi, Wenya Linda, Fennessy, Fiona M., Sponer, Nicole, Johnson, Diana, Laycock, Joanne, Shafi, Seema, Czyzewska-Khan, Justyna, Rowan, Andrew, Chambers, Tim, Matthews, Nik, Turajlic, Samra, Hiley, Crispin, Lee, Siow Ming, Forster, Martin D., Ahmad, Tanya, Falzon, Mary, Borg, Elaine, Lawrence, David, Hayward, Martin, Kolvekar, Shyam, Panagiotopoulos, Nikolaos, Janes, Sam M., Thakrar, Ricky, Ahmed, Asia, Blackhall, Fiona, Summers, Yvonne, Hafez, Dina, Naik, Ashwini, Ganguly, Apratim, Kareht, Stephanie, Shah, Rajesh, Joseph, Leena, Marie Quinn, Anne, Crosbie, Phil A., Naidu, Babu, Middleton, Gary, Langman, Gerald, Trotter, Simon, Nicolson, Marianne, Remmen, Hardy, Kerr, Keith, Chetty, Mahendran, Gomersall, Lesley, Fennell, Dean A., Nakas, Apostolos, Rathinam, Sridhar, Anand, Girija, Khan, Sajid, Russell, Peter, Ezhil, Veni, Ismail, Babikir, Irvin-Sellers, Melanie, Prakash, Vineet, Lester, Jason F., Kornaszewska, Malgorzata, Attanoos, Richard, Adams, Haydn, Davies, Helen, Oukrif, Dahmane, Akarca, Ayse U., Hartley, John A., Lowe, Helen L., Lock, Sara, Iles, Natasha, Bell, Harriet, Ngai, Yenting, Elgar, Greg, Szallasi, Zoltan, Schwarz, Roland F., Herrero, Javier, Stewart, Aengus, Quezada, Sergio A., Peggs, Karl S., Van Loo, Peter, Dive, Caroline, Lin, C. Jimmy, Rabinowitz, Matthew, Aerts, Hugo J. W. L., Hackshaw, Allan, Shaw, Jacqui A., Zimmermann, Bernhard G., Swanton, Charles, Bosshard-Carter, Leticia, Goh, Gerald, Gorman, Pat, Murugaesu, Nirupa, Hynds, Robert E., Horswell, Stuart, Bakir, Maise Al, Mitter, Richard, Escudero, Mickael, Xu, Hang, Goldman, Jacki, Stone, Richard Kevin, Denner, Tamara, Biggs, Jennifer, Costa, Marta, Begum, Sharmin, Phillimore, Ben, Nye, Emma, Graca, Sofia, Joshi, Kroopa, Furness, Andrew, Ben Aissa, Assma, Wong, Yien Ning Sophia, Georgiou, Andy, Simeon, Celia, Hector, Gemma, Smith, Amy, Aranda, Marie, Novelli, Marco, Papadatos-Pastos, Dionysis, Carnell, Dawn, Mendes, Ruheena, George, Jeremy, Navani, Neal, Taylor, Magali, Choudhary, Junaid, Califano, Raffaele, Taylor, Paul, Krysiak, Piotr, Rammohan, Kendadai, Fontaine, Eustace, Booton, Richard, Evison, Matthew, Moss, Stuart, Idries, Faiza, Bishop, Paul, Chaturvedi, Anshuman, Quinn, Anne Marie, Doran, Helen, Leek, Angela, Harrison, Phil, Moore, Katrina, Waddington, Rachael, Novasio, Juliette, Rogan, Jane, Smith, Elaine, Tugwood, Jonathan, Brady, Ged, Rothwell, Dominic G., Chemi, Francesca, Pierce, Jackie, Gulati, Sakshi, Bellamy, Mary, Bancroft, Hollie, Kerr, Amy, Kadiri, Salma, Webb, Joanne, Djearaman, Madava, Quesne, John Le, Thomas, Anne, Walter, Harriet, Monteiro, William, Marshall, Hilary, Nelson, Louise, Bennett, Jonathan, Primrose, Lindsay, Amadi, Anita, Palmer, Shirley, Miller, Joy, Buchan, Keith, Edwards, Alison, Morgan, Fiona, Verjee, Azmina, MacKenzie, Mairead, Wilcox, Maggie, Smith, Sean, Gower, Nicole, Ottensmeier, Christian, Chee, Serena, Johnson, Benjamin, Alzetani, Aiman, Shaw, Emily, Lim, Eric, De Sousa, Paulo, Barbosa, Monica Tavares, Bowman, Alex, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Proli, Chiara, Cufari, Maria Elena, Ronquillo, John Carlo, Kwayie, Angela, Bhayani, Harshil, Hamilton, Morag, Bakar, Yusura, Mensah, Natalie, Ambrose, Lyn, Devaraj, Anand, Buderi, Silviu, Finch, Jonathan, Azcarate, Leire, Chavan, Hema, Green, Sophie, Mashinga, Hillaria, Nicholson, Andrew G., Lau, Kelvin, Sheaff, Michael, Schmid, Peter, Conibear, John, Light, Teresa, Horey, Tracey, Danson, Sarah, Bury, Jonathan, Edwards, John, Hill, Jennifer, Matthews, Sue, Kitsanta, Yota, Suvarna, Kim, Fisher, Patricia, Keerio, Allah Dino, Shackcloth, Michael, Gosney, John, Postmus, Pieter, Feeney, Sarah, Asante-Siaw, Julius, Dentro, Stefan, and Dessimoz, Christophe
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Lung cancer -- Genetic aspects -- Development and progression ,DNA sequencing -- Methods ,Phylogeny -- Observations ,Cancer metastasis -- Genetic aspects ,Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies., Author(s): Christopher Abbosh [1]; Nicolai J. Birkbak [1, 2]; Gareth A. Wilson [1, 2]; Mariam Jamal-Hanjani [1]; Tudor Constantin [3]; Raheleh Salari [3]; John Le Quesne [4]; David A. Moore [...]
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- 2017
- Full Text
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5. Cellules CAR-T pour le traitement des tumeurs solides : présent et futur
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Ben Aissa, Assma, Niculescu, Maria-Viviana, and Migliorini, Denis
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ddc:616 ,Neoplasms / therapy ,Antigens, Neoplasm ,T-Lymphocytes ,Receptors, Antigen, T-Cell ,Tumor Microenvironment ,Humans ,General Medicine ,Receptors, Chimeric Antigen / genetics ,Immunotherapy, Adoptive - Abstract
La thérapie cellulaire adoptive par cellules CAR-T (CAR-T cells, Chimeric Antigen Receptor T-cells) permet de modifier génétique-ment des lymphocytes T de telle sorte qu'ils expriment un nouveau récepteur capable de cibler des antigènes tumoraux spécifiques. Cette thérapie montre des résultats impressionnants dans certaines hémopathies malignes mais rencontre encore de nombreux obstacles dans le traitement des tumeurs solides. En effet, la paucité des cibles antigéniques, l'hétérogénéité antigénique, la difficulté d'accès au site tumoral et le microenvironnement tumoral immunosuppressif constituent les principaux défis à surmonter dans les tumeurs solides. L'avancement rapide des technologies CAR couplé à une meilleure compréhension des mécanismes d'efficacité, toxicité et résistance tracent le chemin du succès des cellules CAR-T dans les tumeurs solides.
- Published
- 2021
6. Expansion of airway basal epithelial cells from primary human non‐small cell lung cancer tumors
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Hynds, Robert E., Ben Aissa, Assma, Gowers, Kate H.C., Watkins, Thomas B.K., Bosshard‐Carter, Leticia, Rowan, Andrew J., Veeriah, Selvaraju, Wilson, Gareth A., Quezada, Sergio A., Swanton, Charles, and Janes, Sam M.
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Male ,basal cells ,Lung Neoplasms ,Pyridines ,Short Report ,Respiratory Mucosa ,Molecular Cancer Biology ,Mice ,Carcinoma, Non-Small-Cell Lung ,Tumor Cells, Cultured ,Animals ,Humans ,stem/progenitor cells ,Aged ,Cell Proliferation ,Aged, 80 and over ,cell culture ,High-Throughput Nucleotide Sequencing ,Epithelial Cells ,3T3 Cells ,Sequence Analysis, DNA ,Middle Aged ,Amides ,Coculture Techniques ,lung cancer ,Neoplasm Transplantation - Abstract
Pre‐clinical non‐small cell lung cancer (NSCLC) models are poorly representative of the considerable inter‐ and intra‐tumor heterogeneity of the disease in patients. Primary cell‐based in vitro models of NSCLC are therefore desirable for novel therapy development and personalized cancer medicine. Methods have been described to generate rapidly proliferating epithelial cell cultures from multiple human epithelia using 3T3‐J2 feeder cell culture in the presence of Y‐27632, a RHO‐associated protein kinase (ROCK) inhibitor, in what are known as “conditional reprograming conditions” (CRC) or 3T3 + Y. In some cancer studies, variations of this methodology have allowed primary tumor cell expansion across a number of cancer types but other studies have demonstrated the preferential expansion of normal epithelial cells from tumors in such conditions. Here, we report our experience regarding the derivation of primary NSCLC cell cultures from 12 lung adenocarcinoma patients enrolled in the Tracking Cancer Evolution through Therapy (TRACERx) clinical study and discuss these in the context of improving the success rate for in vitro cultivation of cells from NSCLC tumors., What's new? Traditionally, the primary culture of human cancer cells has been challenging. A new protocol known as 3T3 + Y has allowed cancer cell cultures to be established across multiple cancer types, but reports are inconsistent for non‐small cell lung cancer (NSCLC). Here, the authors sought to expand tumor cells from surgically resected primary human lung adenocarcinoma tumors within the TRACERx clinical study using 3T3 + Y. Contaminating normal epithelial cells were the predominant cell type in early passage cultures, although KRAS‐mutant tumor cells were cultured in one donor culture. The researchers urge caution in the use of NSCLC primary cell cultures and call for further investigation in 3T3 + Y applications.
- Published
- 2018
7. Spatial heterogeneity of the T cell receptor repertoire reflects the mutational landscape in lung cancer
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Joshi, Kroopa, Robert de Massy, Marc, Ismail, Mazlina, Reading, James L., Uddin, Imran, Woolston, Annemarie, Hatipoglu, Emine, Oakes, Theres, Rosenthal, Rachel, Peacock, Thomas, Ronel, Tahel, Noursadeghi, Mahdad, Turati, Virginia, Georgiou, Andrew, Furness, Andrew J. S., Wong, Yien Ning Sophia, Ben Aissa, Assma, Werner Sunderland, Mariana, Jamal-Hanjani, Mariam, Veeriah, Selvaraju, Birkbak, Nicolai Juul, Wilson, Gareth A., Hiley, Crispin T, Ghorani, Ehsan, Guerra-Assunção, José Afonso, Herrero, Javier, Enver, Tariq, Hadrup, Sine R., Hackshaw, Allan, Peggs, Karl S, McGranahan, Nicholas, Swanton, Charles, Quezada, Sergio A., Chain, Benny, Joshi, Kroopa, Robert de Massy, Marc, Ismail, Mazlina, Reading, James L., Uddin, Imran, Woolston, Annemarie, Hatipoglu, Emine, Oakes, Theres, Rosenthal, Rachel, Peacock, Thomas, Ronel, Tahel, Noursadeghi, Mahdad, Turati, Virginia, Georgiou, Andrew, Furness, Andrew J. S., Wong, Yien Ning Sophia, Ben Aissa, Assma, Werner Sunderland, Mariana, Jamal-Hanjani, Mariam, Veeriah, Selvaraju, Birkbak, Nicolai Juul, Wilson, Gareth A., Hiley, Crispin T, Ghorani, Ehsan, Guerra-Assunção, José Afonso, Herrero, Javier, Enver, Tariq, Hadrup, Sine R., Hackshaw, Allan, Peggs, Karl S, McGranahan, Nicholas, Swanton, Charles, Quezada, Sergio A., and Chain, Benny
- Abstract
Somatic mutations together with immunoediting drive extensive heterogeneity within non-small-cell lung cancer (NSCLC). Herein we examine heterogeneity of the T cell antigen receptor (TCR) repertoire. The number of TCR sequences selectively expanded in tumors varies within and between tumors and correlates with the number of nonsynonymous mutations. Expanded TCRs can be subdivided into TCRs found in all tumor regions (ubiquitous) and those present in a subset of regions (regional). The number of ubiquitous and regional TCRs correlates with the number of ubiquitous and regional nonsynonymous mutations, respectively. Expanded TCRs form part of clusters of TCRs of similar sequence, suggestive of a spatially constrained antigen-driven process. CD8+ tumor-infiltrating lymphocytes harboring ubiquitous TCRs display a dysfunctional tissue-resident phenotype. Ubiquitous TCRs are preferentially detected in the blood at the time of tumor resection as compared to routine follow-up. These findings highlight a noninvasive method to identify and track relevant tumor-reactive TCRs for use in adoptive T cell immunotherapy.
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- 2019
8. Fc effector function contributes to the activity of human anti-CTLA-4 antibodies
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Arce Vargas, Frederick, Furness, Andrew J.S., Litchfield, Kevin, Joshi, Kroopa, Rosenthal, Rachel, Ghorani, Ehsan, Solomon, Isabelle, Lesko, Marta H., Ruef, Nora, Roddie, Claire, Henry, Jake Y., Spain, Lavinia, Ben Aissa, Assma, Georgiou, Andrew, Wong, Yien Ning Sophia, Smith, Myles, Strauss, Dirk, Hayes, Andrew, Nicol, David, O'Brien, Tim, Mårtensson, Linda, Ljungars, Anne, Teige, Ingrid, Frendéus, Björn, Pule, Martin, Marafioti, Teresa, Gore, Martin, Larkin, James, Turajlic, Samra, Swanton, Charles, Peggs, Karl S., Quezada, Sergio A., Harrington, Kevin, Melcher, Alan, Wotherspoon, Andrew, Francis, Nicholas, Challacombe, Ben, Fernando, Archana, Hazell, Steve, Chandra, Ashish, Pickering, Lisa, Lynch, Joanna, Rudman, Sarah, Chowdhury, Simon, Harrison-Phipps, Karen, Varia, Mary, Horsfield, Catherine, Polson, Alexander, Stamp, Gordon, O'Donnell, Marie, Drake, William, Hill, Peter, Hrouda, David, Mayer, Eric, Olsburgh, Jonathan, Kooiman, Gordon, O'Connor, Kevin, Stewart, Grant, Aitchison, Michael, Tran, Maxine, Fotiadis, Nicos, Verma, Hema, Lopez, Jose, Lester, Jason, Morgan, Fiona, Kornaszewska, Malgorzata, Attanoos, Richard, Adams, Haydn, Davies, Helen, Fennell, Dean, Shaw, Jacqui, Le Quesne, John, Nakas, Apostolos, Rathinam, Sridhar, Monteiro, William, Marshall, Hilary, Nelson, Louise, Bennett, Jonathan, Riley, Joan, Primrose, Lindsay, Martinson, Luke, Anand, Girija, Khan, Sajid, Nicolson, Marianne, Kerr, Keith, Palmer, Shirley, Remmen, Hardy, Miller, Joy, Buchan, Keith, Chetty, Mahendran, Gomersall, Lesley, Lock, Sara, Naidu, Babu, Langman, Gerald, Trotter, Simon, Bellamy, Mary, Bancroft, Hollie, Kerr, Amy, Kadiri, Salma, Webb, Joanne, Middleton, Gary, Djearaman, Madava, Summers, Yvonne, Califano, Raffaele, Taylor, Paul, Shah, Rajesh, Krysiak, Piotr, Rammohan, Kendadai, Fontaine, Eustace, Booton, Richard, Evison, Matthew, Crosbie, Phil, Moss, Stuart, Idries, Faiza, Novasio, Juliette, Joseph, Leena, Bishop, Paul, Chaturvedi, Anshuman, Marie Quinn, Anne, Doran, Helen, leek, Angela, Harrison, Phil, Moore, Katrina, Waddington, Rachael, Blackhall, Fiona, Rogan, Jane, Smith, Elaine, Dive, Caroline, Brady, Ged, Rothwell, Dominic, Gulati, Sakshi, Chemie, Francesca, Tugwood, Jonathan, Pierce, Jackie, Lawrence, David, Hayward, Martin, Panagiotopoulos, Nikolaos, George, Robert, Patrini, Davide, Falzon, Mary, Borg, Elaine, Khiroya, Reena, Jamal-Hanjani, Mariam, Wilson, Gareth, Juul Birkbak, Nicolai, Watkins, Thomas, McGranahan, Nicholas, Abbosh, Christopher, Horswell, Stuart, Mitter, Richard, Escudero, Mickael, Stewart, Aengus, Rowan, Andrew, Hiley, Crispin, Goldman, Jacki, Ahmed, Asia, Taylor, Magali, Choudhary, Junaid, Shaw, Penny, Veeriah, Raju, Czyzewska-Khan, Justyna, Johnson, Diana, Laycock, Joanne, Hynds, Robert, Werner Sunderland, Mariana, Reading, James, Novelli, Marco, Oukrif, Dahmane, Janes, Sam, Forster, Martin, Ahmad, Tanya, Ming Lee, Siow, van Loo, Peter, Herrero, Javier, Hartley, John, Kevin Stone, Richard, Denner, Tamara, Costa, Marta, Begum, Sharmin, Phillimore, Ben, Chambers, Tim, Nye, Emma, Ward, Sophie, Elgar, Greg, Al-Bakir, Maise, Carnell, Dawn, Mendes, Ruheena, George, Jeremy, Navani, Neal, Papadatos-Pastos, Dionysis, Scarci, Marco, Gorman, Pat, Lowe, Helen, Ensell, Leah, Moore, David, MacKenzie, Mairead, Wilcox, Maggie, Bell, Harriet, Hackshaw, Allan, Ngai, Yenting, Smith, Sean, Gower, Nicole, Ottensmeier, Christian, Chee, Serena, Johnson, Benjamin, Alzetani, Aiman, Shaw, Emily, Lim, Eric, De Sousa, Paulo, Tavares Barbosa, Monica, Nicholson, Andrew, Bowman, Alex, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Proli, Chiara, Elena Cufari, Maria, Carlo Ronquillo, John, Kwayie, Angela, Bhayani, Harshil, Hamilton, Morag, Bakar, Yusura, Mensah, Natalie, Ambrose, Lyn, Devaraj, Anand, Buderi, Silviu, Finch, Jonathan, Azcarate, Leire, Chavan, Hema, Green, Sophie, Mashinga, Hillaria, Lau, Kelvin, Sheaff, Michael, Schmid, Peter, Conibear, John, Ezhil, Veni, Prakash, Vineet, Danson, Sarah, Bury, Jonathan, Edwards, John, Hill, Jennifer, Matthews, Sue, Kitsanta, Yota, Suvarna, Kim, Shackcloth, Michael, Gosney, John, Postmus, Pieter, Feeney, Sarah, Asante-Siaw, Julius, Russell, Peter, Light, Teresa, Horey, Tracey, Blyth, Kevin, Dick, Craig, and Kirk, Alan
- Abstract
With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches.
- Published
- 2018
9. Association of the imbalance between early and late differentiated intra-tumor CD4 T cells with mutational burden in non-small cell lung cancer.
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Ghorani, Ehsan, primary, Reading, James L., additional, Henry, Jake Y., additional, Robert De Massy, Marc, additional, Rosenthal, Rachel, additional, Furness, Andrew J.S., additional, Ben Aissa, Assma, additional, Jamal-Hanjani, Mariam, additional, Birkbak, Nicolai, additional, Wilson, Gareth, additional, Salgado, Roberto, additional, Lund, Tom, additional, Hiley, Crispin T., additional, Loi, Sherene, additional, Hackshaw, Allan, additional, McGranahan, Nicholas, additional, Chain, Benjamin M., additional, Peggs, Karl S., additional, Swanton, Charles, additional, and Quezada, Sergio A., additional
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- 2019
- Full Text
- View/download PDF
10. Fc-Optimized Anti-CD25 depletes tumor-infiltrating regulatory T Cells and synergizes with PD-1 Blockade to eradicate established tumors
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Arce Vargas, Frederick, Furness, Andrew J.S., Solomon, Isabelle, Joshi, Kroopa, Mekkaoui, Leila, Lesko, Marta H., Miranda Rota, Enrique, Dahan, Rony, Georgiou, Andrew, Sledzinska, Anna, Ben Aissa, Assma, Franz, Dafne, Werner Sunderland, Mariana, Wong, Yien Ning Sophia, Henry, Jake Y., O’Brien, Tim, Nicol, David, Challacombe, Ben, Beers, Stephen A., Turajlic, Samra, Gore, Martin, Larkin, James, Swanton, Charles, Chester, Kerry A., Pule, Martin, Ravetch, Jeffrey V., Marafioti, Teresa, Peggs, Karl S., Quezada, Sergio A., Spain, Lavinia, Wotherspoon, Andrew, Francis, Nicholas, Smith, Myles, Strauss, Dirk, Hayes, Andrew, Soultati, Aspasia, Stares, Mark, Lynch, Joanna, Fotiadis, Nicos, Fernando, Archana, Hazell, Steve, Chandra, Ashish, Pickering, Lisa, Rudman, Sarah, Chowdhury, Simon, Jamal-Hanjani, Mariam, Veeriah, Selvaraju, Shafi, Seema, Czyzewska-Khan, Justyna, Johnson, Diana, Laycock, Joanne, Bosshard-Carter, Leticia, Goh, Gerald, Rosenthal, Rachel, Gorman, Pat, Murugaesu, Nirupa, Hynds, Robert E., Wilson, Gareth, Birkbak, Nicolai J., Watkins, Thomas B.K., McGranahan, Nicholas, Horswell, Stuart, Mitter, Richard, Escudero, Mickael, Stewart, Aengus, Van Loo, Peter, Rowan, Andrew, Xu, Hang, Hiley, Crispin, Abbosh, Christopher, Goldman, Jacki, Stone, Richard Kevin, Denner, Tamara, Matthews, Nik, Elgar, Greg, Ward, Sophia, Biggs, Jennifer, Costa, Marta, Begum, Sharmin, Phillimore, Ben, Chambers, Tim, Nye, Emma, Graca, Sofia, Al Bakir, Maise, Hartley, John A., Lowe, Helen L., Herrero, Javier, Lawrence, David, Hayward, Martin, Panagiotopoulos, Nikolaos, Kolvekar, Shyam, Falzon, Mary, Borg, Elaine, Simeon, Celia, Hector, Gemma, Smith, Amy, Aranda, Marie, Novelli, Marco, Oukrif, Dahmane, Janes, Sam M., Thakrar, Ricky, Forster, Martin, Ahmad, Tanya, Lee, Siow Ming, Papadatos-Pastos, Dionysis, Carnell, Dawn, Mendes, Ruheena, George, Jeremy, Navani, Neal, Ahmed, Asia, Taylor, Magali, Choudhary, Junaid, Summers, Yvonne, Califano, Raffaele, Taylor, Paul, Shah, Rajesh, Krysiak, Piotr, Rammohan, Kendadai, Fontaine, Eustace, Booton, Richard, Evison, Matthew, Crosbie, Phil, Moss, Stuart, Idries, Faiza, Joseph, Leena, Bishop, Paul, Chaturved, Anshuman, Quinn, Anne Marie, Doran, Helen, Leek, Angela, Harrison, Phil, Moore, Katrina, Waddington, Rachael, Novasio, Juliette, Blackhall, Fiona, Rogan, Jane, Smith, Elaine, Dive, Caroline, Tugwood, Jonathan, Brady, Ged, Rothwell, Dominic G., Chemi, Francesca, Pierce, Jackie, Gulati, Sakshi, Naidu, Babu, Langman, Gerald, Trotter, Simon, Bellamy, Mary, Bancroft, Hollie, Kerr, Amy, Kadiri, Salma, Webb, Joanne, Middleton, Gary, Djearaman, Madava, Fennell, Dean, Shaw, Jacqui A., Le Quesne, John, Moore, David, Nakas, Apostolos, Rathinam, Sridhar, Monteiro, William, Marshall, Hilary, Nelson, Louise, Bennett, Jonathan, Riley, Joan, Primrose, Lindsay, Martinson, Luke, Anand, Girija, Khan, Sajid, Amadi, Anita, Nicolson, Marianne, Kerr, Keith, Palmer, Shirley, Remmen, Hardy, Miller, Joy, Buchan, Keith, Chetty, Mahendran, Gomersall, Lesley, Lester, Jason, Edwards, Alison, Morgan, Fiona, Adams, Haydn, Davies, Helen, Kornaszewska, Malgorzata, Attanoos, Richard, Lock, Sara, Verjee, Azmina, MacKenzie, Mairead, Wilcox, Maggie, Bell, Harriet, Iles, Natasha, Hackshaw, Allan, Ngai, Yenting, Smith, Sean, Gower, Nicole, Ottensmeier, Christian, Chee, Serena, Johnson, Benjamin, Alzetani, Aiman, Shaw, Emily, Lim, Eric, De Sousa, Paulo, Barbosa, Monica Tavares, Bowman, Alex, Jorda, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Proli, Chiara, Cufari, Maria Elena, Ronquillo, John Carlo, Kwayie, Angela, Bhayani, Harshil, Hamilton, Morag, Bakar, Yusura, Mensah, Natalie, Ambrose, Lyn, Devaraj, Anand, Buderi, Silviu, Finch, Jonathan, Azcarate, Leire, Chavan, Hema, Green, Sophie, Mashinga, Hillaria, Nicholson, Andrew G., Lau, Kelvin, Sheaff, Michael, Schmid, Peter, Conibear, John, Ezhil, Veni, Ismail, Babikir, Irvin-sellers, Melanie, Prakash, Vineet, Russell, Peter, Light, Teresa, Horey, Tracey, Danson, Sarah, Bury, Jonathan, Edwards, John, Hill, Jennifer, Matthews, Sue, Kitsanta, Yota, Suvarna, Kim, Fisher, Patricia, Keerio, Allah Dino, Shackcloth, Michael, Gosney, John, Postmus, Pieter, Feeney, Sarah, and Asante-Siaw, Julius
- Subjects
hemic and immune systems ,chemical and pharmacologic phenomena ,R1 - Abstract
Summary\ud \ud CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology.
- Published
- 2017
11. Urine-derived lymphocytes as a non-invasive measure of the bladder tumor immune microenvironment
- Author
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Wong, Yien Ning Sophia, primary, Joshi, Kroopa, additional, Khetrapal, Pramit, additional, Ismail, Mazlina, additional, Reading, James L., additional, Sunderland, Mariana Werner, additional, Georgiou, Andrew, additional, Furness, Andrew J.S., additional, Ben Aissa, Assma, additional, Ghorani, Ehsan, additional, Oakes, Theres, additional, Uddin, Imran, additional, Tan, Wei Shen, additional, Feber, Andrew, additional, McGovern, Ursula, additional, Swanton, Charles, additional, Freeman, Alex, additional, Marafioti, Teresa, additional, Briggs, Timothy P., additional, Kelly, John D., additional, Powles, Thomas, additional, Peggs, Karl S., additional, Chain, Benjamin M., additional, Linch, Mark D., additional, and Quezada, Sergio A., additional
- Published
- 2018
- Full Text
- View/download PDF
12. Characterisation of the TCR repertoire in NSCLC to reveal the relationship between TCR heterogeneity and genetic heterogeneity that is influenced by mutational load and is associated with disease recurrence.
- Author
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Joshi, Kroopa, primary, Ismail, Mazlina, additional, Reading, James L, additional, Robert De Massy, Marc, additional, Uddin, Imran, additional, Jamal-Hanjani, Mariam, additional, Veeriah, Selvaraju, additional, Oakes, Theres, additional, Wong, Yien Ning Sophia, additional, Furness, Andrew James Scott, additional, Ghorani, Ehsan, additional, Georgiou, Andrew, additional, Beastall, Carmella, additional, Mangal, Nagina, additional, Ben Aissa, Assma, additional, Werner Sunderland, Mariana, additional, Peggs, Karl, additional, Swanton, Charles, additional, Chain, Benjamin, additional, and Quezada, Sergio A, additional
- Published
- 2018
- Full Text
- View/download PDF
13. Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution
- Author
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McGranahan, Nicholas, primary, Rosenthal, Rachel, additional, Hiley, Crispin T., additional, Rowan, Andrew J., additional, Watkins, Thomas B.K., additional, Wilson, Gareth A., additional, Birkbak, Nicolai J., additional, Veeriah, Selvaraju, additional, Van Loo, Peter, additional, Herrero, Javier, additional, Swanton, Charles, additional, Jamal-Hanjani, Mariam, additional, Shafi, Seema, additional, Czyzewska-Khan, Justyna, additional, Johnson, Diana, additional, Laycock, Joanne, additional, Bosshard-Carter, Leticia, additional, Gorman, Pat, additional, Hynds, Robert E., additional, Wilson, Gareth, additional, McGranahan, Nicholas, additional, Horswell, Stuart, additional, Mitter, Richard, additional, Escudero, Mickael, additional, Stewart, Aengus, additional, Rowan, Andrew, additional, Xu, Hang, additional, Turajlic, Samra, additional, Hiley, Crispin, additional, Abbosh, Christopher, additional, Goldman, Jacki, additional, Stone, Richard Kevin, additional, Denner, Tamara, additional, Matthews, Nik, additional, Elgar, Greg, additional, Ward, Sophia, additional, Costa, Marta, additional, Begum, Sharmin, additional, Phillimore, Ben, additional, Chambers, Tim, additional, Nye, Emma, additional, Graca, Sofia, additional, Al Bakir, Maise, additional, Joshi, Kroopa, additional, Furness, Andrew, additional, Ben Aissa, Assma, additional, Wong, Yien Ning Sophia, additional, Georgiou, Andy, additional, Quezada, Sergio, additional, Hartley, John A., additional, Lowe, Helen L., additional, Lawrence, David, additional, Hayward, Martin, additional, Panagiotopoulos, Nikolaos, additional, Kolvekar, Shyam, additional, Falzon, Mary, additional, Borg, Elaine, additional, Marafioti, Teresa, additional, Simeon, Celia, additional, Hector, Gemma, additional, Smith, Amy, additional, Aranda, Marie, additional, Novelli, Marco, additional, Oukrif, Dahmane, additional, Janes, Sam M., additional, Thakrar, Ricky, additional, Forster, Martin, additional, Ahmad, Tanya, additional, Lee, Siow Ming, additional, Papadatos-Pastos, Dionysis, additional, Carnell, Dawn, additional, Mendes, Ruheena, additional, George, Jeremy, additional, Navani, Neal, additional, Ahmed, Asia, additional, Taylor, Magali, additional, Choudhary, Junaid, additional, Summers, Yvonne, additional, Califano, Raffaele, additional, Taylor, Paul, additional, Shah, Rajesh, additional, Krysiak, Piotr, additional, Rammohan, Kendadai, additional, Fontaine, Eustace, additional, Booton, Richard, additional, Evison, Matthew, additional, Crosbie, Phil, additional, Moss, Stuart, additional, Idries, Faiza, additional, Joseph, Leena, additional, Bishop, Paul, additional, Chaturved, Anshuman, additional, Quinn, Anne Marie, additional, Doran, Helen, additional, Leek, Angela, additional, Harrison, Phil, additional, Moore, Katrina, additional, Waddington, Rachael, additional, Novasio, Juliette, additional, Blackhall, Fiona, additional, Rogan, Jane, additional, Smith, Elaine, additional, Dive, Caroline, additional, Tugwood, Jonathan, additional, Brady, Ged, additional, Rothwell, Dominic G., additional, Chemi, Francesca, additional, Pierce, Jackie, additional, Gulati, Sakshi, additional, Naidu, Babu, additional, Langman, Gerald, additional, Trotter, Simon, additional, Bellamy, Mary, additional, Bancroft, Hollie, additional, Kerr, Amy, additional, Kadiri, Salma, additional, Webb, Joanne, additional, Middleton, Gary, additional, Djearaman, Madava, additional, Fennell, Dean, additional, Shaw, Jacqui A., additional, Le Quesne, John, additional, Moore, David, additional, Nakas, Apostolos, additional, Rathinam, Sridhar, additional, Monteiro, William, additional, Marshall, Hilary, additional, Nelson, Louise, additional, Bennett, Jonathan, additional, Riley, Joan, additional, Primrose, Lindsay, additional, Martinson, Luke, additional, Anand, Girija, additional, Khan, Sajid, additional, Amadi, Anita, additional, Nicolson, Marianne, additional, Kerr, Keith, additional, Palmer, Shirley, additional, Remmen, Hardy, additional, Miller, Joy, additional, Buchan, Keith, additional, Chetty, Mahendran, additional, Gomersall, Lesley, additional, Lester, Jason, additional, Edwards, Alison, additional, Morgan, Fiona, additional, Adams, Haydn, additional, Davies, Helen, additional, Kornaszewska, Malgorzata, additional, Attanoos, Richard, additional, Lock, Sara, additional, Verjee, Azmina, additional, MacKenzie, Mairead, additional, Wilcox, Maggie, additional, Bell, Harriet, additional, Hackshaw, Allan, additional, Ngai, Yenting, additional, Smith, Sean, additional, Gower, Nicole, additional, Ottensmeier, Christian, additional, Chee, Serena, additional, Johnson, Benjamin, additional, Alzetani, Aiman, additional, Shaw, Emily, additional, Lim, Eric, additional, De Sousa, Paulo, additional, Barbosa, Monica Tavares, additional, Bowman, Alex, additional, Jordan, Simon, additional, Rice, Alexandra, additional, Raubenheimer, Hilgardt, additional, Proli, Chiara, additional, Cufari, Maria Elena, additional, Ronquillo, John Carlo, additional, Kwayie, Angela, additional, Bhayani, Harshil, additional, Hamilton, Morag, additional, Bakar, Yusura, additional, Mensah, Natalie, additional, Ambrose, Lyn, additional, Devaraj, Anand, additional, Buderi, Silviu, additional, Finch, Jonathan, additional, Azcarate, Leire, additional, Chavan, Hema, additional, Green, Sophie, additional, Mashinga, Hillaria, additional, Nicholson, Andrew G., additional, Lau, Kelvin, additional, Sheaff, Michael, additional, Schmid, Peter, additional, Conibear, John, additional, Ezhil, Veni, additional, Ismail, Babikir, additional, Irvin-sellers, Melanie, additional, Prakash, Vineet, additional, Russell, Peter, additional, Light, Teresa, additional, Horey, Tracey, additional, Danson, Sarah, additional, Bury, Jonathan, additional, Edwards, John, additional, Hill, Jennifer, additional, Matthews, Sue, additional, Kitsanta, Yota, additional, Suvarna, Kim, additional, Fisher, Patricia, additional, Keerio, Allah Dino, additional, Shackcloth, Michael, additional, Gosney, John, additional, Postmus, Pieter, additional, Feeney, Sarah, additional, Asante-Siaw, Julius, additional, Aerts, Hugo J.W.L., additional, Dentro, Stefan, additional, and Dessimoz, Christophe, additional
- Published
- 2017
- Full Text
- View/download PDF
14. Defining the mechanisms of response and resistance to anti-PD-1 therapy: An exploratory phase II study of pembrolizumab in advanced melanoma (ADAPTeM).
- Author
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Joshi, Kroopa, primary, Furness, Andrew J.S., additional, Oakes, Theres, additional, Heather, James, additional, Spain, Lavinia Anne, additional, Wong, Yien Ning Sophia, additional, Ben Aissa, Assma, additional, Stares, Mark, additional, Smith, Myles JF, additional, Strauss, Dirk C, additional, Hayes, Andrew J, additional, Marafioti, Teresa, additional, Turajlic, Samra, additional, Gore, Martin Eric, additional, Peggs, Karl, additional, Chain, Benjamin, additional, Quezada, Sergio, additional, and Larkin, James M. G., additional
- Published
- 2016
- Full Text
- View/download PDF
15. Anticancéreux sous haute tension
- Author
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Ben Aissa, Assma, George, A-C, El M'Rabet, F Z, Mach, Nicolas, Dietrich, P-Y, and Pechere, Antoinette
- Subjects
ddc:616 ,Evidence-Based Medicine ,Risk Factors ,Angiogenesis Inhibitors/administration & dosage/adverse effects ,Hypertension/chemically induced/physiopathology ,Humans ,Albuminuria/chemically induced/physiopathology ,Risk Assessment ,Vascular Endothelial Growth Factor A/drug effects ,Algorithms ,ddc:613 ,Kidney Diseases/chemically induced ,Neoplasms/drug therapy - Abstract
Angiogenesis inhibitor drugs, targeting VEGF (vascular endothelial growth factor) are used increasingly in oncology for a wide range of advanced cancers (colorectal cancer, lung cancer, renal cell cancer,...). Generally, they are well tolerated but cardiovascular and renal side effects may appear. The most frequent complications are hypertension and proteinuria which, very often, remain asymptomatic. Therefore, they have to be searched for systematically before and during the treatment. Sometimes, anti-hypertensive medication is needed. We are just beginning to understand the pathophysiological mechanisms of antiangiogenic therapies. Only a multidisciplinary approach will improve our knowledge of those target agents and allow a better management of the cancer patient.
- Published
- 2011
16. Publisher Correction: Spatial heterogeneity of the T cell receptor repertoire reflects the mutational landscape in lung cancer
- Author
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Joshi, Kroopa, de Massy, Marc Robert, Ismail, Mazlina, Reading, James L., Uddin, Imran, Woolston, Annemarie, Hatipoglu, Emine, Oakes, Theres, Rosenthal, Rachel, Peacock, Thomas, Ronel, Tahel, Noursadeghi, Mahdad, Turati, Virginia, Furness, Andrew J. S., Georgiou, Andrew, Wong, Yien Ning Sophia, Ben Aissa, Assma, Sunderland, Mariana Werner, Jamal-Hanjani, Mariam, Veeriah, Selvaraju, Birkbak, Nicolai J., Wilson, Gareth A., Hiley, Crispin T., Ghorani, Ehsan, Guerra-Assunção, José Afonso, Herrero, Javier, Enver, Tariq, Hadrup, Sine R., Hackshaw, Allan, Peggs, Karl S., McGranahan, Nicholas, Swanton, Charles, Quezada, Sergio A., and Chain, Benny
- Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
- Published
- 2020
- Full Text
- View/download PDF
17. [Therapeutic cancer vaccines: challenges and perspectives].
- Author
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Colarusso G, Mechahougui H, and Ben Aissa A
- Subjects
- Humans, Cancer Vaccines administration & dosage, Neoplasms therapy, Neoplasms immunology, Neoplasms prevention & control, Immunotherapy methods, Immunotherapy trends
- Abstract
For over a decade, immunotherapy has been transforming cancer treatment and prognosis. Tumor therapeutic vaccines trigger new immune responses and enhance existing immunity to more effectively combat cancer. These vaccines aim to curb the established disease or prevent recurrence, unlike conventional preventive vaccines. There are four categories of therapeutic vaccines: cellular, viral/bacterial, peptide, and nucleic acid, each with its own benefits and challenges. Advances in the understanding of anti-tumor immunity and advanced technologies such as mRNA vaccines support the development of this new treatment option. Currently in clinical trials, they could lead to promising and personalised anti-cancer therapies., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.
- Published
- 2024
- Full Text
- View/download PDF
18. Spatial heterogeneity of the T cell receptor repertoire reflects the mutational landscape in lung cancer.
- Author
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Joshi K, de Massy MR, Ismail M, Reading JL, Uddin I, Woolston A, Hatipoglu E, Oakes T, Rosenthal R, Peacock T, Ronel T, Noursadeghi M, Turati V, Furness AJS, Georgiou A, Wong YNS, Ben Aissa A, Sunderland MW, Jamal-Hanjani M, Veeriah S, Birkbak NJ, Wilson GA, Hiley CT, Ghorani E, Guerra-Assunção JA, Herrero J, Enver T, Hadrup SR, Hackshaw A, Peggs KS, McGranahan N, Swanton C, Quezada SA, and Chain B
- Subjects
- Aged, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes pathology, Carcinoma, Non-Small-Cell Lung immunology, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Non-Small-Cell Lung therapy, Female, Humans, Lymphocytes, Tumor-Infiltrating immunology, Lymphocytes, Tumor-Infiltrating pathology, Male, Middle Aged, Mutation, Receptors, Antigen, T-Cell immunology, Carcinoma, Non-Small-Cell Lung genetics, Genetic Heterogeneity, Immunotherapy, Adoptive, Receptors, Antigen, T-Cell genetics
- Abstract
Somatic mutations together with immunoediting drive extensive heterogeneity within non-small-cell lung cancer (NSCLC). Herein we examine heterogeneity of the T cell antigen receptor (TCR) repertoire. The number of TCR sequences selectively expanded in tumors varies within and between tumors and correlates with the number of nonsynonymous mutations. Expanded TCRs can be subdivided into TCRs found in all tumor regions (ubiquitous) and those present in a subset of regions (regional). The number of ubiquitous and regional TCRs correlates with the number of ubiquitous and regional nonsynonymous mutations, respectively. Expanded TCRs form part of clusters of TCRs of similar sequence, suggestive of a spatially constrained antigen-driven process. CD8
+ tumor-infiltrating lymphocytes harboring ubiquitous TCRs display a dysfunctional tissue-resident phenotype. Ubiquitous TCRs are preferentially detected in the blood at the time of tumor resection as compared to routine follow-up. These findings highlight a noninvasive method to identify and track relevant tumor-reactive TCRs for use in adoptive T cell immunotherapy.- Published
- 2019
- Full Text
- View/download PDF
19. Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.
- Author
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Arce Vargas F, Furness AJS, Litchfield K, Joshi K, Rosenthal R, Ghorani E, Solomon I, Lesko MH, Ruef N, Roddie C, Henry JY, Spain L, Ben Aissa A, Georgiou A, Wong YNS, Smith M, Strauss D, Hayes A, Nicol D, O'Brien T, Mårtensson L, Ljungars A, Teige I, Frendéus B, Pule M, Marafioti T, Gore M, Larkin J, Turajlic S, Swanton C, Peggs KS, and Quezada SA
- Subjects
- Animals, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal pharmacology, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Immunological pharmacology, CTLA-4 Antigen antagonists & inhibitors, Cell Line, Tumor, Female, Humans, Ipilimumab administration & dosage, Ipilimumab pharmacology, Melanoma genetics, Melanoma immunology, Mice, Receptors, IgG metabolism, Treatment Outcome, Xenograft Model Antitumor Assays, Antineoplastic Agents, Immunological administration & dosage, Melanoma drug therapy, Polymorphism, Single Nucleotide, Receptors, IgG genetics, T-Lymphocytes, Regulatory immunology
- Abstract
With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8
+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF
20. Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors.
- Author
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Arce Vargas F, Furness AJS, Solomon I, Joshi K, Mekkaoui L, Lesko MH, Miranda Rota E, Dahan R, Georgiou A, Sledzinska A, Ben Aissa A, Franz D, Werner Sunderland M, Wong YNS, Henry JY, O'Brien T, Nicol D, Challacombe B, Beers SA, Turajlic S, Gore M, Larkin J, Swanton C, Chester KA, Pule M, Ravetch JV, Marafioti T, Peggs KS, and Quezada SA
- Subjects
- Animals, Antibodies, Monoclonal metabolism, Antibodies, Monoclonal therapeutic use, Cell Line, Tumor, Flow Cytometry, Humans, Immunotherapy methods, K562 Cells, Kaplan-Meier Estimate, Lymphocyte Depletion, Mice, Neoplasms pathology, Neoplasms therapy, Programmed Cell Death 1 Receptor antagonists & inhibitors, Programmed Cell Death 1 Receptor metabolism, Protein Binding immunology, Receptors, IgG immunology, Receptors, IgG metabolism, T-Lymphocytes, Regulatory metabolism, Antibodies, Monoclonal immunology, Immunoglobulin Fc Fragments immunology, Interleukin-2 Receptor alpha Subunit immunology, Neoplasms immunology, Programmed Cell Death 1 Receptor immunology, T-Lymphocytes, Regulatory immunology
- Abstract
CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
21. [HPV-related cancer: should young men be vaccinated?].
- Author
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Ben Aissa A and Mach N
- Subjects
- Adolescent, Carcinoma, Squamous Cell immunology, Carcinoma, Squamous Cell mortality, Carcinoma, Squamous Cell prevention & control, Child, Female, Human papillomavirus 16 immunology, Human papillomavirus 16 pathogenicity, Human papillomavirus 18 immunology, Human papillomavirus 18 pathogenicity, Humans, Male, Papillomavirus Infections complications, Papillomavirus Infections immunology, Papillomavirus Infections transmission, Precancerous Conditions etiology, Precancerous Conditions prevention & control, Sex Factors, Uterine Cervical Neoplasms immunology, Uterine Cervical Neoplasms mortality, Uterine Cervical Dysplasia immunology, Uterine Cervical Dysplasia mortality, Human papillomavirus 16 physiology, Human papillomavirus 18 physiology, Papillomavirus Infections prevention & control, Uterine Cervical Neoplasms prevention & control, Vaccination methods, Uterine Cervical Dysplasia prevention & control
- Abstract
HPV infection, a sexually transmissible disease, causes squamous cell carcinoma in a small fraction of infected individuals, years after exposure. Several cancers both in female and male, such as cervical cancer, anal carcinoma and up to 50% of oropharyngeal tumors are related to serotypes 16 and 18 of HPV. Several studies evaluating vaccination of young women before HPV exposure showed very good protection against cervical dysplasia and carcinoma in situ. Health authorities' guidelines now widely recommend vaccination of female between 11 and 14 years old. Results of recent trials also reveal good protective effect in men, raising the question of immunizing both young women and men. Important medical and socio-economic issues will need to be addressed before implementing such program.
- Published
- 2012
22. [Is lung cancer in women different?].
- Author
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Ben Aissa A and Mach N
- Subjects
- Carcinoma, Non-Small-Cell Lung diagnosis, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung therapy, Female, Humans, Lung Neoplasms diagnosis, Lung Neoplasms genetics, Lung Neoplasms therapy, Male, Mutation physiology, Prognosis, Treatment Outcome, Carcinoma, Non-Small-Cell Lung epidemiology, Lung Neoplasms epidemiology, Sex Characteristics
- Abstract
Lung cancer is the leading cause of cancer death in the world, favored by smoking. Nonsmall cell lung cancer is a heterogeneous disease whose prevalence is increasing among women. Epidemiological, hormonal and pathological factors explain tumor differences between men and women. Women have more frequently adenocarcinomas, EGFR mutations and respond better to cancer treatments. In recent decades, many advances have been made, allowing us to move from histological to molecular characterization of lung tumors. Further analysis of gender disparities will help us to understand and improve the management of patients with NSCLC.
- Published
- 2012
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