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1. CEA-CD3 bispecific antibody cibisatamab with or without atezolizumab in patients with CEA-positive solid tumours: results of two multi-institutional Phase 1 trials

Author

Segal, Neil H., Melero, Ignacio, Moreno, Victor, Steeghs, Neeltje, Marabelle, Aurelien, Rohrberg, Kristoffer, Rodriguez-Ruiz, Maria E., Eder, Joseph P., Eng, Cathy, Manji, Gulam A., Waterkamp, Daniel, Leutgeb, Barbara, Bouseida, Said, Flinn, Nick, Das Thakur, Meghna, Elze, Markus C., Koeppen, Hartmut, Jamois, Candice, Martin-Facklam, Meret, Lieu, Christopher H., Calvo, Emiliano, Paz-Ares, Luis, Tabernero, Josep, and Argilés, Guillem

Published
2024
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2. Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial

Author

Ascierto, Paolo A., Casula, Milena, Bulgarelli, Jenny, Pisano, Marina, Piccinini, Claudia, Piccin, Luisa, Cossu, Antonio, Mandalà, Mario, Ferrucci, Pier Francesco, Guidoboni, Massimo, Rutkowski, Piotr, Ferraresi, Virginia, Arance, Ana, Guida, Michele, Maiello, Evaristo, Gogas, Helen, Richtig, Erika, Fierro, Maria Teresa, Lebbe, Celeste, Helgadottir, Hildur, Queirolo, Paola, Spagnolo, Francesco, Tucci, Marco, Del Vecchio, Michele, Cao, Maria Gonzales, Minisini, Alessandro Marco, De Placido, Sabino, Sanmamed, Miguel F., Mallardo, Domenico, Paone, Miriam, Vitale, Maria Grazia, Melero, Ignacio, Grimaldi, Antonio M., Giannarelli, Diana, Dummer, Reinhard, Sileni, Vanna Chiarion, and Palmieri, Giuseppe

Published
2024
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3. Central Role of the Antigen-Presentation and Interferon-γ Pathways in Resistance to Immune Checkpoint Blockade

Author

Paschen, Annette, Melero, Ignacio, and Ribas, Antoni

Subjects
Vaccine Related, Immunization, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Inflammatory and immune system, interferon-gamma, major histocompatibility complex, JAK, immunoresistance, checkpoint inhibitors, tumor microenvironment
Abstract

Resistance to immunotherapy is due in some instances to the acquired stealth mechanisms of tumor cells that lose expression of MHC class I antigen–presenting molecules or downregulate their class I antigen–presentation pathways. Most dramatically, biallelic β2-microglobulin (B2M) loss leads to complete loss of MHC class I expression and to invisibility to CD8+ T cells. MHC class I expression and antigen presentation are potently upregulated by interferon-γ (IFNγ) in a manner that depends on IFNγ receptor (IFNGR) signaling via JAK1 and JAK2. Mutations in these molecules lead to IFNγ unresponsiveness and mediate loss of recognition and killing by cytotoxic T lymphocytes. Loss of MHC class I augments sensitivity of tumor cells to be killed by natural killer (NK) lymphocytes, and this mechanism could be exploited to revert resistance, for instance, with interleukin-2 (IL-2)-based agents. Moreover, in some experimental models,potent local type I interferon responses, such as those following intratumoral injection of Toll-like receptor 9 (TLR9) or TLR3 agonists, revert resistance due to mutations of JAKs.

Published
2022

4. Whole exome sequencing and machine learning germline analysis of individuals presenting with extreme phenotypes of high and low risk of developing tobacco-associated lung adenocarcinoma

Author

Patiño-García, Ana, Guruceaga, Elizabeth, Andueza, Maria Pilar, Ocón, Marimar, Fodop Sokoudjou, Jafait Junior, de Villalonga Zornoza, Nicolás, Alkorta-Aranburu, Gorka, Uria, Ibon Tamayo, Gurpide, Alfonso, Camps, Carlos, Jantus-Lewintre, Eloísa, Navamuel-Andueza, Maria, Sanmamed, Miguel F., Melero, Ignacio, Elgendy, Mohamed, Fusco, Juan Pablo, Zulueta, Javier J., de-Torres, Juan P., Bastarrika, Gorka, Seijo, Luis, Pio, Ruben, Montuenga, Luis M., Hernáez, Mikel, Ochoa, Idoia, and Perez-Gracia, Jose Luis

Published
2024
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6. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of hepatocellular carcinoma

Author

Greten, Tim F, Abou-Alfa, Ghassan K, Cheng, Ann-Lii, Duffy, Austin G, El-Khoueiry, Anthony B, Finn, Richard S, Galle, Peter R, Goyal, Lipika, He, Aiwu Ruth, Kaseb, Ahmed O, Kelley, Robin Kate, Lencioni, Riccardo, Lujambio, Amaia, Hrones, Donna Mabry, Pinato, David J, Sangro, Bruno, Troisi, Roberto I, Woods, Andrea Wilson, Yau, Thomas, Zhu, Andrew X, and Melero, Ignacio

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Clinical Trials and Supportive Activities, Liver Cancer, Digestive Diseases, Rare Diseases, Vaccine Related, Cancer, Clinical Research, Liver Disease, Chronic Liver Disease and Cirrhosis, Patient Safety, Immunization, Good Health and Well Being, Carcinoma, Hepatocellular, Guidelines as Topic, Humans, Immunotherapy, Liver Neoplasms, antineoplastic protocols, immunotherapy, guidelines as topic, liver neoplasms, Oncology and carcinogenesis
Abstract

Patients with advanced hepatocellular carcinoma (HCC) have historically had few options and faced extremely poor prognoses if their disease progressed after standard-of-care tyrosine kinase inhibitors (TKIs). Recently, the standard of care for HCC has been transformed as a combination of the immune checkpoint inhibitor (ICI) atezolizumab plus the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab was shown to offer improved overall survival in the first-line setting. Immunotherapy has demonstrated safety and efficacy in later lines of therapy as well, and ongoing trials are investigating novel combinations of ICIs and TKIs, in addition to interventions earlier in the course of disease or in combination with liver-directed therapies. Because HCC usually develops against a background of cirrhosis, immunotherapy for liver tumors is complex and oncologists need to account for both immunological and hepatological considerations when developing a treatment plan for their patients. To provide guidance to the oncology community on important concerns for the immunotherapeutic care of HCC, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel of experts to develop a clinical practice guideline (CPG). The expert panel drew on the published literature as well as their clinical experience to develop recommendations for healthcare professionals on these important aspects of immunotherapeutic treatment for HCC, including diagnosis and staging, treatment planning, immune-related adverse events (irAEs), and patient quality of life (QOL) considerations. The evidence- and consensus-based recommendations in this CPG are intended to give guidance to cancer care providers treating patients with HCC.

Published
2021

7. DNGR-1 limits Flt3L-mediated antitumor immunity by restraining tumor-infiltrating type I conventional dendritic cells.

Author

Cueto, Francisco J, Del Fresno, Carlos, Brandi, Paola, Combes, Alexis J, Hernández-García, Elena, Sánchez-Paulete, Alfonso R, Enamorado, Michel, Bromley, Christian P, Gomez, Manuel J, Conde-Garrosa, Ruth, Mañes, Santos, Zelenay, Santiago, Melero, Ignacio, Iborra, Salvador, Krummel, Matthew F, and Sancho, David

Subjects
CCL5, Cancer, DNGR-1/Clec9a, Flt3L, cDC1, dendritic cells, immunomodulation, immunotherapy, maraviroc
Abstract

BackgroundConventional type 1 dendritic cells (cDC1s) are central to antitumor immunity and their presence in the tumor microenvironment associates with improved outcomes in patients with cancer. DNGR-1 (CLEC9A) is a dead cell-sensing receptor highly restricted to cDC1s. DNGR-1 has been involved in both cross-presentation of dead cell-associated antigens and processes of disease tolerance, but its role in antitumor immunity has not been clarified yet.MethodsB16 and MC38 tumor cell lines were inoculated subcutaneously into wild-type (WT) and DNGR-1-deficient mice. To overexpress Flt3L systemically, we performed gene therapy through the hydrodynamic injection of an Flt3L-encoding plasmid. To characterize the immune response, we performed flow cytometry and RNA-Seq of tumor-infiltrating cDC1s.ResultsHere, we found that cross-presentation of tumor antigens in the steady state was DNGR-1-independent. However, on Flt3L systemic overexpression, tumor growth was delayed in DNGR-1-deficient mice compared with WT mice. Of note, this protection was recapitulated by anti-DNGR-1-blocking antibodies in mice following Flt3L gene therapy. This improved antitumor immunity was associated with Batf3-dependent enhanced accumulation of CD8+ T cells and cDC1s within tumors. Mechanistically, the deficiency in DNGR-1 boosted an Flt3L-induced specific inflammatory gene signature in cDC1s, including Ccl5 expression. Indeed, the increased infiltration of cDC1s within tumors and their protective effect rely on CCL5/CCR5 chemoattraction. Moreover, FLT3LG and CCL5 or CCR5 gene expression signatures correlate with an enhanced cDC1 signature and a favorable overall survival in patients with cancer. Notably, cyclophosphamide elevated serum Flt3L levels and, in combination with the absence of DNGR-1, synergized against tumor growth.ConclusionDNGR-1 limits the accumulation of tumor-infiltrating cDC1s promoted by Flt3L. Thus, DNGR-1 blockade may improve antitumor immunity in tumor therapy settings associated to high Flt3L expression.

Published
2021

9. mRNAs encoding IL-12 and a decoy-resistant variant of IL-18 synergize to engineer T cells for efficacious intratumoral adoptive immunotherapy

Author

Olivera, Irene, Bolaños, Elixabet, Gonzalez-Gomariz, Jose, Hervas-Stubbs, Sandra, Mariño, Karina V., Luri-Rey, Carlos, Etxeberria, Iñaki, Cirella, Assunta, Egea, Josune, Glez-Vaz, Javier, Garasa, Saray, Alvarez, Maite, Eguren-Santamaria, Iñaki, Guedan, Sonia, Sanmamed, Miguel F., Berraondo, Pedro, Rabinovich, Gabriel A., Teijeira, Alvaro, and Melero, Ignacio

Published
2023
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10. Intratumoral administration of mRNA encoding IL-12-based immunocytokines targeting CSF1R and PD-L1 exert potent antitumor effects while restraining systemic exposure to IL-12

Author

Di Trani, Claudia Augusta, Cirella, Assunta, Arrizabalaga, Leire, Alvarez, Maite, Bella, Ángela, Fernandez-Sendin, Myriam, Russo-Cabrera, Joan Salvador, Gomar, Celia, Ardaiz, Nuria, Teijeira, Alvaro, Bolaños, Elixabet, González-Gomariz, José, Otano, Itziar, Aranda, Fernando, Palencia, Belén, Segués, Aina, Huang, Shuyu, van Duijnhoven, Sander M.J., van Elsas, Andrea, Melero, Ignacio, and Berraondo, Pedro

Published
2023
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11. Intratumoral immunotherapy with mRNAs encoding chimeric protein constructs encompassing IL-12, CD137 agonists and TGF-β antagonists.

Author

Cirella, Assunta, Bolaños, Elixabet, Luri-Rey, Carlos, Di Trani, Claudia Augusta, Olivera, Irene, Gomis, Gabriel, Glez-Vaz, Javier, Pinci, Beatrice, Garasa, Saray, Sánchez-Gregorio, Sandra, Azpilikueta, Arantza, Eguren, Iñaki, Valencia, Karmele, Palencia, Belén, Alvarez, Maite, Ochoa, Maria C., Teijeira, Álvaro, Berraondo, Pedro, and Melero, Ignacio

Published
2023
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13. Low-dose ionizing γ-radiation elicits the extrusion of neutrophil extracellular traps

Author

Teijeira, Alvaro, primary, Garasa, Saray, additional, Ochoa, Maria C., additional, Sanchez-Gregorio, Sandra, additional, Gomis, Gabriel, additional, Luri-Rey, Carlos, additional, Martinez-Monge, Rafael, additional, Pinci, Beatrice, additional, Valencia, Karmele, additional, Palencia, Belen, additional, Barbes, Benigno, additional, Bolanos, Elixabet, additional, Azpilikueta, Arantza, additional, Garcia-Cardosa, Marina, additional, Burguete, Javier, additional, Eguren-Santamaria, Iñaki, additional, Garate-Soraluze, Eneko, additional, Berraondo, Pedro, additional, Perez-Gracia, Jose L., additional, de Andrea, Carlos E., additional, Rodriguez-Ruiz, Maria E., additional, and Melero, Ignacio, additional

Published
2024
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14. Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity from a Phase I Study of Simlukafusp Alfa (FAP-IL2v) in Advanced/Metastatic Solid Tumors

Author

Steeghs, Neeltje, primary, Gomez-Roca, Carlos, additional, Rohrberg, Kristoffer S., additional, Mau-Sørensen, Morten, additional, Robbrecht, Debbie, additional, Tabernero, Josep, additional, Ahmed, Samreen, additional, Rodriguez-Ruiz, Maria E., additional, Ardeshir, Caroline, additional, Schmid, Daniela, additional, Sleiman, Nassim, additional, Watson, Carl, additional, Piper-Lepoutre, Hanna, additional, Dejardin, David, additional, Evers, Stefan, additional, Boetsch, Christophe, additional, Charo, Jehad, additional, Teichgräber, Volker, additional, and Melero, Ignacio, additional

Published
2024
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15. Supplementary Methods S1 from Obinutuzumab Pretreatment as a Novel Approach to Mitigate Formation of Anti-Drug Antibodies Against Cergutuzumab Amunaleukin in Patients with Solid Tumors

Author

Peters, Solange, primary, Angevin, Eric, primary, Alonso-Gordoa, Teresa, primary, Rohrberg, Kristoffer, primary, Melero, Ignacio, primary, Mellado, Begoña, primary, Perez-Gracia, Jose-Luis, primary, Tabernero, Josep, primary, Adessi, Celine, primary, Boetsch, Christophe, primary, Watson, Carl, primary, Dal Porto, Joseph, primary, Dejardin, David, primary, Del Nagro, Christopher, primary, Nicolini, Valeria, primary, Evers, Stefan, primary, Klein, Christian, primary, Leutgeb, Barbara, primary, Pisa, Pavel, primary, Rossmann, Eva, primary, Saro, José, primary, Umana, Pablo, primary, Charo, Jehad, primary, Teichgräber, Volker, primary, and Steeghs, Neeltje, primary

Published
2024
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16. Supplementary Figure S2 from Obinutuzumab Pretreatment as a Novel Approach to Mitigate Formation of Anti-Drug Antibodies Against Cergutuzumab Amunaleukin in Patients with Solid Tumors

Author

Peters, Solange, primary, Angevin, Eric, primary, Alonso-Gordoa, Teresa, primary, Rohrberg, Kristoffer, primary, Melero, Ignacio, primary, Mellado, Begoña, primary, Perez-Gracia, Jose-Luis, primary, Tabernero, Josep, primary, Adessi, Celine, primary, Boetsch, Christophe, primary, Watson, Carl, primary, Dal Porto, Joseph, primary, Dejardin, David, primary, Del Nagro, Christopher, primary, Nicolini, Valeria, primary, Evers, Stefan, primary, Klein, Christian, primary, Leutgeb, Barbara, primary, Pisa, Pavel, primary, Rossmann, Eva, primary, Saro, José, primary, Umana, Pablo, primary, Charo, Jehad, primary, Teichgräber, Volker, primary, and Steeghs, Neeltje, primary

Published
2024
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17. Supplementary Table S1 from Obinutuzumab Pretreatment as a Novel Approach to Mitigate Formation of Anti-Drug Antibodies Against Cergutuzumab Amunaleukin in Patients with Solid Tumors

Author

Peters, Solange, primary, Angevin, Eric, primary, Alonso-Gordoa, Teresa, primary, Rohrberg, Kristoffer, primary, Melero, Ignacio, primary, Mellado, Begoña, primary, Perez-Gracia, Jose-Luis, primary, Tabernero, Josep, primary, Adessi, Celine, primary, Boetsch, Christophe, primary, Watson, Carl, primary, Dal Porto, Joseph, primary, Dejardin, David, primary, Del Nagro, Christopher, primary, Nicolini, Valeria, primary, Evers, Stefan, primary, Klein, Christian, primary, Leutgeb, Barbara, primary, Pisa, Pavel, primary, Rossmann, Eva, primary, Saro, José, primary, Umana, Pablo, primary, Charo, Jehad, primary, Teichgräber, Volker, primary, and Steeghs, Neeltje, primary

Published
2024
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18. Data from Obinutuzumab Pretreatment as a Novel Approach to Mitigate Formation of Anti-Drug Antibodies Against Cergutuzumab Amunaleukin in Patients with Solid Tumors

Author

Peters, Solange, primary, Angevin, Eric, primary, Alonso-Gordoa, Teresa, primary, Rohrberg, Kristoffer, primary, Melero, Ignacio, primary, Mellado, Begoña, primary, Perez-Gracia, Jose-Luis, primary, Tabernero, Josep, primary, Adessi, Celine, primary, Boetsch, Christophe, primary, Watson, Carl, primary, Dal Porto, Joseph, primary, Dejardin, David, primary, Del Nagro, Christopher, primary, Nicolini, Valeria, primary, Evers, Stefan, primary, Klein, Christian, primary, Leutgeb, Barbara, primary, Pisa, Pavel, primary, Rossmann, Eva, primary, Saro, José, primary, Umana, Pablo, primary, Charo, Jehad, primary, Teichgräber, Volker, primary, and Steeghs, Neeltje, primary

Published
2024
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19. Efficacy of LCMV-based cancer immunotherapies is unleashed by intratumoral injections of polyI:C

Author

Gomar, Celia, primary, Di Trani, Claudia Augusta, additional, Bella, Angela, additional, Arrizabalaga, Leire, additional, Gonzalez-Gomariz, Jose, additional, Fernandez-Sendin, Myriam, additional, Alvarez, Maite, additional, Russo-Cabrera, Joan Salvador, additional, Ardaiz, Nuria, additional, Aranda, Fernando, additional, Schippers, Timo, additional, Quintero, Marisol, additional, Melero, Ignacio, additional, Orlinger, Klaus K, additional, Lauterbach, Henning, additional, and Berraondo, Pedro, additional

Published
2024
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21. Neutrophil Extracellular Traps, Local IL-8 Expression, and Cytotoxic T-Lymphocyte Response in the Lungs of Patients With Fatal COVID-19

Author

Melero, Ignacio, Villalba-Esparza, María, Recalde-Zamacona, Borja, Jiménez-Sánchez, Daniel, Teijeira, Álvaro, Argueta, Alan, García-Tobar, Laura, Álvarez-Gigli, Laura, Sainz, Cristina, Garcia-Ros, David, Toledo, Estefanía, Abengozar-Muela, Marta, Fernández-Alonso, Mirian, Rodríguez-Mateos, Mariano, Reina, Gabriel, Carmona-Torre, Francisco, Quiroga, Jorge Augusto, Del Pozo, Jose L., Cross, Amy, López-Janeiro, Álvaro, Hardisson, David, Echeveste, José I., Lozano, Maria D., Ho, Ling-Pei, Klenerman, Paul, Issa, Fadi, Landecho, Manuel F., and de Andrea, Carlos E.

Published
2022
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22. Antitumor efficacy and reduced toxicity using an anti-CD137 Probody therapeutic

Author

Etxeberria, Iñaki, Bolaños, Elixabet, Teijeira, Alvaro, Garasa, Saray, Yanguas, Alba, Azpilikueta, Arantza, Kavanaugh, William M., Vasiljeva, Olga, Belvin, Marcia, Howng, Bruce, Irving, Bryan, Tipton, Kimberly, West, James, Mei, Li, Korman, Alan J., Sega, Emanuela, Olivera, Irene, Cirella, Assunta, Ochoa, Maria C., Rodriguez, Maria E., Melero, Ana, Sanmamed, Miguel F., Engelhardt, John J., and Melero, Ignacio

Published
2021

23. Perspectives in Immunotherapy: meeting report from the Immunotherapy Bridge, December 1st–2nd, 2021

Author

Ascierto, Paolo A., Avallone, Antonio, Bhardwaj, Nina, Bifulco, Carlo, Bracarda, Sergio, Brody, Joshua D., Buonaguro, Luigi, Demaria, Sandra, Emens, Leisha A., Ferris, Robert L., Galon, Jérôme, Khleif, Samir N., Klebanoff, Christopher A., Laskowski, Tamara, Melero, Ignacio, Paulos, Chrystal M., Pignata, Sandro, Ruella, Marco, Svane, Inge Marie, Taube, Janis M., Fox, Bernard A., Hwu, Patrick, and Puzanov, Igor

Published
2022
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24. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial

Author

Yau, Thomas, Park, Joong-Won, Finn, Richard S, Cheng, Ann-Lii, Mathurin, Philippe, Edeline, Julien, Kudo, Masatoshi, Harding, James J, Merle, Philippe, Rosmorduc, Olivier, Wyrwicz, Lucjan, Schott, Eckart, Choo, Su Pin, Kelley, Robin Kate, Sieghart, Wolfgang, Assenat, Eric, Zaucha, Renata, Furuse, Junji, Abou-Alfa, Ghassan K, El-Khoueiry, Anthony B, Melero, Ignacio, Begic, Damir, Chen, Gong, Neely, Jaclyn, Wisniewski, Tami, Tschaika, Marina, and Sangro, Bruno

Published
2022
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28. Omentum: Friend or foe in ovarian cancer immunotherapy?

Author

Bella, Ángela, primary, Arrizabalaga, Leire, additional, Di Trani, Claudia Augusta, additional, Fernández-Sendin, Myriam, additional, Teijeira, Alvaro, additional, Russo-Cabrera, Joan Salvador, additional, Melero, Ignacio, additional, Berraondo, Pedro, additional, and Aranda, Fernando, additional

Published
2022
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29. Final results of urelumab, an anti-CD137 agonist monoclonal antibody, in combination with cetuximab or nivolumab in patients with advanced solid tumors

Author

Khushalani, Nikhil I, primary, Ott, Patrick A, additional, Ferris, Robert L, additional, Cascone, Tina, additional, Schadendorf, Dirk, additional, Le, Dung T, additional, Sharma, Manish R, additional, Barlesi, Fabrice, additional, Sharfman, William, additional, Luke, Jason J, additional, Melero, Ignacio, additional, Lathers, Deanne, additional, Neely, Jaclyn, additional, Suryawanshi, Satyendra, additional, Sanyal, Abanti, additional, Holloway, James L, additional, Suryawanshi, Rasika, additional, Ely, Scott, additional, and Segal, Neil H, additional

Published
2024
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31. Obinutuzumab Pretreatment as a Novel Approach to Mitigate Formation of Anti-Drug Antibodies Against Cergutuzumab Amunaleukin in Patients with Solid Tumors

Author

Peters, Solange, primary, Angevin, Eric, additional, Alonso-Gordoa, Teresa, additional, Rohrberg, Kristoffer, additional, Melero, Ignacio, additional, Mellado, Begoña, additional, Perez-Gracia, Jose-Luis, additional, Tabernero, Josep, additional, Adessi, Celine, additional, Boetsch, Christophe, additional, Watson, Carl, additional, Dal Porto, Joseph, additional, Dejardin, David, additional, Del Nagro, Christopher, additional, Nicolini, Valeria, additional, Evers, Stefan, additional, Klein, Christian, additional, Leutgeb, Barbara, additional, Pisa, Pavel, additional, Rossmann, Eva, additional, Saro, José, additional, Umana, Pablo, additional, Charo, Jehad, additional, Teichgräber, Volker, additional, and Steeghs, Neeltje, additional

Published
2024
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34. Immunodynamics: a cancer immunotherapy trials network review of immune monitoring in immuno-oncology clinical trials

Author

Kohrt, Holbrook E, Tumeh, Paul C, Benson, Don, Bhardwaj, Nina, Brody, Joshua, Formenti, Silvia, Fox, Bernard A, Galon, Jerome, June, Carl H, Kalos, Michael, Kirsch, Ilan, Kleen, Thomas, Kroemer, Guido, Lanier, Lewis, Levy, Ron, Lyerly, H Kim, Maecker, Holden, Marabelle, Aurelien, Melenhorst, Jos, Miller, Jeffrey, Melero, Ignacio, Odunsi, Kunle, Palucka, Karolina, Peoples, George, Ribas, Antoni, Robins, Harlan, Robinson, William, Serafini, Tito, Sondel, Paul, Vivier, Eric, Weber, Jeff, Wolchok, Jedd, Zitvogel, Laurence, Disis, Mary L, Cheever, Martin A, and on behalf of the Cancer Immunotherapy Trials Network (CITN)

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Clinical Trials and Supportive Activities, Clinical Research, Vaccine Related, Immunotherapy, Immunization, Cancer, 5.1 Pharmaceuticals, 6.1 Pharmaceuticals, Biomarker, Clinical trial, Cancer Immunotherapy Trials Network, Oncology and carcinogenesis
Abstract

The efficacy of PD-1/PD-L1 targeted therapies in addition to anti-CTLA-4 solidifies immunotherapy as a modality to add to the anticancer arsenal. Despite raising the bar of clinical efficacy, immunologically targeted agents raise new challenges to conventional drug development paradigms by highlighting the limited relevance of assessing standard pharmacokinetics (PK) and pharmacodynamics (PD). Specifically, systemic and intratumoral immune effects have not consistently correlated with standard relationships between systemic dose, toxicity, and efficacy for cytotoxic therapies. Hence, PK and PD paradigms remain inadequate to guide the selection of doses and schedules, both starting and recommended Phase 2 for immunotherapies. The promise of harnessing the immune response against cancer must also be considered in light of unique and potentially serious toxicities. Refining immune endpoints to better inform clinical trial design represents a high priority challenge. The Cancer Immunotherapy Trials Network investigators review the immunodynamic effects of specific classes of immunotherapeutic agents to focus immune assessment modalities and sites, both systemic and importantly intratumoral, which are critical to the success of the rapidly growing field of immuno-oncology.

Published
2016

35. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part one

Author

Lundqvist, Andreas, van Hoef, Vincent, Zhang, Xiaonan, Wennerberg, Erik, Lorent, Julie, Witt, Kristina, Sanz, Laia Masvidal, Liang, Shuo, Murray, Shannon, Larsson, Ola, Kiessling, Rolf, Mao, Yumeng, Sidhom, John-William, Bessell, Catherine A, Havel, Jonathan, Schneck, Jonathan, Chan, Timothy A, Sachsenmeier, Eliot, Woods, David, Berglund, Anders, Ramakrishnan, Rupal, Sodre, Andressa, Weber, Jeffrey, Zappasodi, Roberta, Li, Yanyun, Qi, Jingjing, Wong, Philip, Sirard, Cynthia, Postow, Michael, Newman, Walter, Koon, Henry, Velcheti, Vamsidhar, Callahan, Margaret K, Wolchok, Jedd D, Merghoub, Taha, Lum, Lawrence G, Choi, Minsig, Thakur, Archana, Deol, Abhinav, Dyson, Gregory, Shields, Anthony, Haymaker, Cara, Uemura, Marc, Murthy, Ravi, James, Marihella, Wang, Daqing, Brevard, Julie, Monaghan, Catherine, Swann, Suzanne, Geib, James, Cornfeld, Mark, Chunduru, Srinivas, Agrawal, Sudhir, Yee, Cassian, Wargo, Jennifer, Patel, Sapna P, Amaria, Rodabe, Tawbi, Hussein, Glitza, Isabella, Woodman, Scott, Hwu, Wen-Jen, Davies, Michael A, Hwu, Patrick, Overwijk, Willem W, Bernatchez, Chantale, Diab, Adi, Massarelli, Erminia, Segal, Neil H, Ribrag, Vincent, Melero, Ignacio, Gangadhar, Tara C, Urba, Walter, Schadendorf, Dirk, Ferris, Robert L, Houot, Roch, Morschhauser, Franck, Logan, Theodore, Luke, Jason J, Sharfman, William, Barlesi, Fabrice, Ott, Patrick A, Mansi, Laura, Kummar, Shivaani, Salles, Gilles, Carpio, Cecilia, Meier, Roland, Krishnan, Suba, McDonald, Dan, Maurer, Matthew, Gu, Xuemin, Neely, Jaclyn, Suryawanshi, Satyendra, Levy, Ronald, Khushalani, Nikhil, Wu, Jennifer, Zhang, Jinyu, Basher, Fahmin, Rubinstein, Mark, Bucsek, Mark, and Qiao, Guanxi

Subjects
Good Health and Well Being
Published
2016

41. Intraperitoneal administration of a modified vaccinia virus Ankara confers single-chain interleukin-12 expression to the omentum and achieves immune-mediated efficacy against peritoneal carcinomatosis

Author

Bella, Ángela, primary, Arrizabalaga, Leire, additional, Di Trani, Claudia Augusta, additional, Gonzalez-Gomariz, Jose, additional, Gomar, Celia, additional, Russo-Cabrera, Joan Salvador, additional, Olivera, Irene, additional, Cirella, Assunta, additional, Fernandez-Sendin, Myriam, additional, Alvarez, Maite, additional, Teijeira, Alvaro, additional, Atay, Cigdem, additional, Medina-Echeverz, José, additional, Hinterberger, Maria, additional, Hochrein, Hubertus, additional, Melero, Ignacio, additional, Berraondo, Pedro, additional, and Aranda, Fernando, additional

Published
2023
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42. 617 A Phase I study of a tumor-targeted, fibroblast activation protein (FAP)-CD40 agonist (RO7300490) in patients with advanced solid tumors

Author

Melero, Ignacio, primary, Baradji, Maria Lostes, additional, Spanggaard, Iben, additional, Lee, Dae, additional, Spicer, James, additional, Thistlethwaite, Fiona C, additional, Symeonides, Stefan, additional, Oh, Do-Youn, additional, Hollebecque, Antoine, additional, Rusterholz, Corinne, additional, Cirovic, Olivera, additional, Zhao, Yvonne, additional, Kratochwil, Nicole, additional, Reis, Bernhard, additional, Epp, Alexandra, additional, Kazantzidis, Georgios, additional, and Moreno, Victor, additional

Published
2023
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44. Intratumoral co‐injection of NK cells and NKG2A‐neutralizing monoclonal antibodies

Author

Melero, Ignacio, primary, Ochoa, Maria C, additional, Molina, Carmen, additional, Sanchez‐Gregorio, Sandra, additional, Garasa, Saray, additional, Luri‐Rey, Carlos, additional, Hervas‐Stubbs, Sandra, additional, Casares, Noelia, additional, Elizalde, Edurne, additional, Gomis, Gabriel, additional, Cirella, Assunta, additional, Berraondo, Pedro, additional, Teijeira, Alvaro, additional, and Alvarez, Maite, additional

Published
2023
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45. Future perspectives in melanoma research: meeting report from the “Melanoma Bridge”: Napoli, December 3rd–6th 2014

Author

Ascierto, Paolo A, Atkins, Michael, Bifulco, Carlo, Botti, Gerardo, Cochran, Alistair, Davies, Michael, Demaria, Sandra, Dummer, Reinhard, Ferrone, Soldano, Formenti, Silvia, Gajewski, Thomas F, Garbe, Claus, Khleif, Samir, Kiessling, Rolf, Lo, Roger, Lorigan, Paul, Arthur, Grant Mc, Masucci, Giuseppe, Melero, Ignacio, Mihm, Martin, Palmieri, Giuseppe, Parmiani, Giorgio, Puzanov, Igor, Romero, Pedro, Schilling, Bastian, Seliger, Barbara, Stroncek, David, Taube, Janis, Tomei, Sara, Zarour, Hassane M, Testori, Alessandro, Wang, Ena, Galon, Jérôme, Ciliberto, Gennaro, Mozzillo, Nicola, Marincola, Francesco M, and Thurin, Magdalena

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Vaccine Related, Immunization, Clinical Research, Cancer, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Good Health and Well Being, Biomarkers, Tumor, Humans, Immunotherapy, Italy, Melanoma, Tumor Microenvironment, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract

The fourth "Melanoma Bridge Meeting" took place in Naples, December 3-6th, 2014. The four topics discussed at this meeting were: Molecular and Immunological Advances, Combination Therapies, News in Immunotherapy, and Tumor Microenvironment and Biomarkers. Until recently systemic therapy for metastatic melanoma patients was ineffective, but recent advances in tumor biology and immunology have led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS). New therapies, such as mitogen-activated protein kinase (MAPK) pathway inhibitors as well as other signaling pathway inhibitors, are being tested in patients with metastatic melanoma either as monotherapy or in combination, and all have yielded promising results. These include inhibitors of receptor tyrosine kinases (BRAF, MEK, and VEGFR), the phosphatidylinositol 3 kinase (PI3K) pathway [PI3K, AKT, mammalian target of rapamycin (mTOR)], activators of apoptotic pathway, and the cell cycle inhibitors (CDK4/6). Various locoregional interventions including radiotherapy and surgery are still valid approaches in treatment of advanced melanoma that can be integrated with novel therapies. Intrinsic, adaptive and acquired resistance occur with targeted therapy such as BRAF inhibitors, where most responses are short-lived. Given that the reactivation of the MAPK pathway through several distinct mechanisms is responsible for the majority of acquired resistance, it is logical to combine BRAF inhibitors with inhibitors of targets downstream in the MAPK pathway. For example, combination of BRAF/MEK inhibitors (e.g., dabrafenib/trametinib) have been demonstrated to improve survival compared to monotherapy. Application of novel technologies such sequencing have proven useful as a tool for identification of MAPK pathway-alternative resistance mechanism and designing other combinatorial therapies such as those between BRAF and AKT inhibitors. Improved survival rates have also been observed with immune-targeted therapy for patients with metastatic melanoma. Immune-modulating antibodies came to the forefront with anti-CTLA-4, programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) pathway blocking antibodies that result in durable responses in a subset of melanoma patients. Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors and other approaches such as adoptive cell transfer demonstrate clinical benefit in patients with melanoma as well. These agents are being studied in combination with targeted therapies in attempt to produce longer-term responses than those more typically seen with targeted therapy. Other combinations with cytotoxic chemotherapy and inhibitors of angiogenesis are changing the evolving landscape of therapeutic options and are being evaluated to prevent or delay resistance and to further improve survival rates for this patient population. This meeting's specific focus was on advances in combination of targeted therapy and immunotherapy. Both combination targeted therapy approaches and different immunotherapies were discussed. Similarly to the previous meetings, the importance of biomarkers for clinical application as markers for diagnosis, prognosis and prediction of treatment response was an integral part of the meeting. The overall emphasis on biomarkers supports novel concepts toward integrating biomarkers into contemporary clinical management of patients with melanoma across the entire spectrum of disease stage. Translation of the knowledge gained from the biology of tumor microenvironment across different tumors represents a bridge to impact on prognosis and response to therapy in melanoma.

Published
2015

46. CD137 (4-1BB) costimulation of CD8+ T cells is more potent when provided in cis than in trans with respect to CD3-TCR stimulation

Author

Otano, Itziar, Azpilikueta, Arantza, Glez-Vaz, Javier, Alvarez, Maite, Medina-Echeverz, José, Cortés-Domínguez, Ivan, Ortiz-de-Solorzano, Carlos, Ellmark, Peter, Fritzell, Sara, Hernandez-Hoyos, Gabriela, Nelson, Michelle Hase, Ochoa, María Carmen, Bolaños, Elixabet, Cuculescu, Doina, Jaúregui, Patricia, Sanchez-Gregorio, Sandra, Etxeberria, Iñaki, Rodriguez-Ruiz, María E., Sanmamed, Miguel F., Teijeira, Álvaro, Berraondo, Pedro, and Melero, Ignacio

Published
2021
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48. Elevated serum interleukin-8 is associated with enhanced intratumor neutrophils and reduced clinical benefit of immune-checkpoint inhibitors

Author

Schalper, Kurt A., Carleton, Michael, Zhou, Ming, Chen, Tian, Feng, Ye, Huang, Shu-Pang, Walsh, Alice M., Baxi, Vipul, Pandya, Dimple, Baradet, Timothy, Locke, Darren, Wu, Qiuyan, Reilly, Timothy P., Phillips, Penny, Nagineni, Venkata, Gianino, Nicole, Gu, Jianlei, Zhao, Hongyu, Perez-Gracia, Jose Luis, Sanmamed, Miguel F., and Melero, Ignacio

Published
2020
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