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873 results on '"Maus, Marcela V."'

6. Latent human herpesvirus 6 is reactivated in CAR T cells

Author

Lareau, Caleb A., Yin, Yajie, Maurer, Katie, Sandor, Katalin D., Daniel, Bence, Yagnik, Garima, Peña, José, Crawford, Jeremy Chase, Spanjaart, Anne M., Gutierrez, Jacob C., Haradhvala, Nicholas J., Riberdy, Janice M., Abay, Tsion, Stickels, Robert R., Verboon, Jeffrey M., Liu, Vincent, Buquicchio, Frank A., Wang, Fangyi, Southard, Jackson, Song, Ren, Li, Wenjing, Shrestha, Aastha, Parida, Laxmi, Getz, Gad, Maus, Marcela V., Li, Shuqiang, Moore, Alison, Roberts, Zachary J., Ludwig, Leif S., Talleur, Aimee C., Thomas, Paul G., Dehghani, Houman, Pertel, Thomas, Kundaje, Anshul, Gottschalk, Stephen, Roth, Theodore L., Kersten, Marie J., Wu, Catherine J., Majzner, Robbie G., and Satpathy, Ansuman T.

Published
2023
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7. Phase 1 study of CAR-37 T cells in patients with relapsed or refractory CD37+ lymphoid malignancies

Author

Frigault, Matthew J., Graham, Charlotte E., Berger, Trisha R., Ritchey, Julie, Horick, Nora K., El-Jawahri, Areej, Scarfò, Irene, Schmidts, Andrea, Haradhvala, Nicholas J., Wehrli, Marc, Lee, Won-Ho, Parker, Aiyana L., Wiggin, Hadley R., Bouffard, Amanda, Dey, Aonkon, Leick, Mark B., Katsis, Katelin, Elder, Eva L., Dolaher, Maria A., Cook, Daniella T., Chekmasova, Alena A., Huang, Lu, Nikiforow, Sarah, Daley, Heather, Ritz, Jerome, Armant, Myriam, Preffer, Fred, DiPersio, John F., Nardi, Valentina, Chen, Yi-Bin, Gallagher, Kathleen M. E., and Maus, Marcela V.

Published
2024
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8. Idecabtagene vicleucel for relapsed and refractory multiple myeloma: post hoc 18-month follow-up of a phase 1 trial

Author

Lin, Yi, Raje, Noopur S., Berdeja, Jesús G., Siegel, David S., Jagannath, Sundar, Madduri, Deepu, Liedtke, Michaela, Rosenblatt, Jacalyn, Maus, Marcela V., Massaro, Monica, Petrocca, Fabio, Yeri, Ashish, Finney, Olivia, Caia, Andrea, Yang, Zhihong, Martin, Nathan, Campbell, Timothy B., Rytlewski, Julie, Fuller, Jaymes, Hege, Kristen, Munshi, Nikhil C., and Kochenderfer, James N.

Published
2023
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9. Leukemia-intrinsic determinants of CAR-T response revealed by iterative in vivo genome-wide CRISPR screening

Author

Ramos, Azucena, Koch, Catherine E., Liu-Lupo, Yunpeng, Hellinger, Riley D., Kyung, Taeyoon, Abbott, Keene L., Fröse, Julia, Goulet, Daniel, Gordon, Khloe S., Eidell, Keith P., Leclerc, Paul, Whittaker, Charles A., Larson, Rebecca C., Muscato, Audrey J., Yates, Kathleen B., Dubrot, Juan, Doench, John G., Regev, Aviv, Vander Heiden, Matthew G., Maus, Marcela V., Manguso, Robert T., Birnbaum, Michael E., and Hemann, Michael T.

Published
2023
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12. Genetic retargeting of E3 ligases to enhance CAR T cell therapy

Author

Lane, Isabel C., Kembuan, Gabriele, Carreiro, Jeannie, Kann, Michael C., Lin, William, Bouffard, Amanda A., Kreuzer, Johannes, Morris, Robert, Schneider, Emily M., Kim, Joanna Y., Zou, Charles, Salas-Benito, Diego, Gasser, Jessica A., Leick, Mark B., Słabicki, Mikołaj, Haas, Wilhelm, Maus, Marcela V., and Jan, Max

Published
2024
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13. The 2020 BMT CTN Myeloma Intergroup Workshop on Immune Profiling and Minimal Residual Disease Testing in Multiple Myeloma

Author

Holstein, Sarah A, Bahlis, Nizar, Bergsagel, P Leif, Bhutani, Manisha, Bolli, Niccolo, Brownstein, Carrie, Demolis, Pierre, Foureau, David, Gay, Francesca, Ghobrial, Irene M, Gormley, Nicole, Hillengass, Jens, Kaiser, Martin, Maus, Marcela V, Melenhorst, J Joseph, Merz, Maximilian, Dwyer, Michael O, Paiva, Bruno, Pasquini, Marcelo C, Shah, Nina, Wong, Sandy W, Usmani, Saad Z, and McCarthy, Philip L

Subjects
Transplantation, Rare Diseases, Cancer, Hematology, Good Health and Well Being, Humans, Bone Marrow, Diterpenes, High-Throughput Nucleotide Sequencing, Multiple Myeloma, Neoplasm, Residual, Minimal residual disease, Immune profiling, Multiple myeloma, Endpoint, CAR T-cell, Cellular therapy
Abstract

The fifth annual Blood and Marrow Transplant Clinical Trials Network Myeloma Intergroup Workshop on Immune Profiling and Minimal Residual Disease Testing in Multiple Myeloma was conducted as one of the American Society of Hematology Annual Meeting Scientific Workshops on Thursday December 3, 2020. This workshop focused on four main topics: (1) integrating minimal residual disease into clinical trial design and practice; (2) the molecular and immunobiology of disease evolution and progression in myeloma; (3) adaptation of next-generation sequencing, next-generation flow cytometry, and cytometry by time of flight techniques; and (4) chimeric antigen receptor T-cell and other cellular therapies for myeloma. In this report, we provide a summary of the workshop presentations and discuss future directions in the field.

Published
2021

16. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events

Author

Maus, Marcela V, Alexander, Sara, Bishop, Michael R, Brudno, Jennifer N, Callahan, Colleen, Davila, Marco L, Diamonte, Claudia, Dietrich, Jorg, Fitzgerald, Julie C, Frigault, Matthew J, Fry, Terry J, Holter-Chakrabarty, Jennifer L, Komanduri, Krishna V, Lee, Daniel W, Locke, Frederick L, Maude, Shannon L, McCarthy, Philip L, Mead, Elena, Neelapu, Sattva S, Neilan, Tomas G, Santomasso, Bianca D, Shpall, Elizabeth J, Teachey, David T, Turtle, Cameron J, Whitehead, Tom, and Grupp, Stephan A

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Pediatric, Immunization, Cancer, Biotechnology, Clinical Research, Patient Safety, Vaccine Related, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Drug-Related Side Effects and Adverse Reactions, Guidelines as Topic, Humans, Immunologic Factors, Immunotherapy, Retrospective Studies, adoptive, cell engineering, chimeric antigen, guidelines as topic, hematological neoplasms, immunotherapy, receptors, Oncology and carcinogenesis
Abstract

Immune effector cell (IEC) therapies offer durable and sustained remissions in significant numbers of patients with hematological cancers. While these unique immunotherapies have improved outcomes for pediatric and adult patients in a number of disease states, as 'living drugs,' their toxicity profiles, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), differ markedly from conventional cancer therapeutics. At the time of article preparation, the US Food and Drug Administration (FDA) has approved tisagenlecleucel, axicabtagene ciloleucel, and brexucabtagene autoleucel, all of which are IEC therapies based on genetically modified T cells engineered to express chimeric antigen receptors (CARs), and additional products are expected to reach marketing authorization soon and to enter clinical development in due course. As IEC therapies, especially CAR T cell therapies, enter more widespread clinical use, there is a need for clear, cohesive recommendations on toxicity management, motivating the Society for Immunotherapy of Cancer (SITC) to convene an expert panel to develop a clinical practice guideline. The panel discussed the recognition and management of common toxicities in the context of IEC treatment, including baseline laboratory parameters for monitoring, timing to onset, and pharmacological interventions, ultimately forming evidence- and consensus-based recommendations to assist medical professionals in decision-making and to improve outcomes for patients.

Published
2020

17. Distinct cellular dynamics associated with response to CAR-T therapy for refractory B cell lymphoma

Author

Haradhvala, Nicholas J., Leick, Mark B., Maurer, Katie, Gohil, Satyen H., Larson, Rebecca C., Yao, Ning, Gallagher, Kathleen M. E., Katsis, Katelin, Frigault, Matthew J., Southard, Jackson, Li, Shuqiang, Kann, Michael C., Silva, Harrison, Jan, Max, Rhrissorrakrai, Kahn, Utro, Filippo, Levovitz, Chaya, Jacobs, Raquel A., Slowik, Kara, Danysh, Brian P., Livak, Kenneth J., Parida, Laxmi, Ferry, Judith, Jacobson, Caron, Wu, Catherine J., Getz, Gad, and Maus, Marcela V.

Published
2022
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18. Biology of CAR-T Cells

Author

Berger, Trisha R., Boardman, Alexander, Brentjens, Renier, Maus, Marcela V., Teicher, Beverly A., Series Editor, Ghobadi, Armin, editor, and DiPersio, John F., editor

Published
2022
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21. Comparative analysis of Bcl-2 family protein overexpression in CAR T cells alone and in combination with BH3 mimetics

Author

Korell, Felix, primary, Olson, Michael L., additional, Salas-Benito, Diego, additional, Leick, Mark B., additional, Larson, Rebecca C., additional, Bouffard, Amanda, additional, Silva, Harrison, additional, Gasparetto, Alessandro, additional, Berger, Trisha R., additional, Kann, Michael C., additional, Mergen, Markus, additional, Kienka, Tamina, additional, Wehrli, Marc, additional, Haradhvala, Nicholas J., additional, Bailey, Stefanie R., additional, Letai, Anthony, additional, and Maus, Marcela V., additional

Published
2024
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23. Correction: Chimeric Antigen Receptor T Cells Targeting CD79b Show Efficacy in Lymphoma with or without Cotargeting CD19

Author

Ormhøj, Maria, primary, Scarfò, Irene, additional, Cabral, Maria L., additional, Bailey, Stefanie R., additional, Lorrey, Selena J., additional, Bouffard, Amanda A., additional, Castano, Ana P., additional, Larson, Rebecca C., additional, Riley, Lauren S., additional, Schmidts, Andrea, additional, Choi, Bryan D., additional, Andersen, Rikke S., additional, Cédile, Oriane, additional, Nyvold, Charlotte G., additional, Christensen, Jacob H., additional, Gjerstorff, Morten F., additional, Ditzel, Henrik J., additional, Weinstock, David M., additional, Barington, Torben, additional, Frigault, Matthew J., additional, and Maus, Marcela V., additional

Published
2024
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24. Supplementary Video S12 from Mesothelin CAR T Cells Secreting Anti-FAP/Anti-CD3 Molecules Efficiently Target Pancreatic Adenocarcinoma and its Stroma

Author

Wehrli, Marc, primary, Guinn, Samantha, primary, Birocchi, Filippo, primary, Kuo, Adam, primary, Sun, Yi, primary, Larson, Rebecca C., primary, Almazan, Antonio J., primary, Scarfò, Irene, primary, Bouffard, Amanda A., primary, Bailey, Stefanie R., primary, Anekal, Praju Vikas, primary, Montero Llopis, Paula, primary, Nieman, Linda T., primary, Song, Yuhui, primary, Xu, Katherine H., primary, Berger, Trisha R., primary, Kann, Michael C., primary, Leick, Mark B., primary, Silva, Harrison, primary, Salas-Benito, Diego, primary, Kienka, Tamina, primary, Grauwet, Korneel, primary, Armstrong, Todd D., primary, Zhang, Rui, primary, Zhu, Qingfeng, primary, Fu, Juan, primary, Schmidts, Andrea, primary, Korell, Felix, primary, Jan, Max, primary, Choi, Bryan D., primary, Liss, Andrew S., primary, Boland, Genevieve M., primary, Ting, David T., primary, Burkhart, Richard A., primary, Jenkins, Russell W., primary, Zheng, Lei, primary, Jaffee, Elizabeth M., primary, Zimmerman, Jacquelyn W., primary, and Maus, Marcela V., primary

Published
2024
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25. Supplementary Figure S6 from Mesothelin CAR T Cells Secreting Anti-FAP/Anti-CD3 Molecules Efficiently Target Pancreatic Adenocarcinoma and its Stroma

Author

Wehrli, Marc, primary, Guinn, Samantha, primary, Birocchi, Filippo, primary, Kuo, Adam, primary, Sun, Yi, primary, Larson, Rebecca C., primary, Almazan, Antonio J., primary, Scarfò, Irene, primary, Bouffard, Amanda A., primary, Bailey, Stefanie R., primary, Anekal, Praju Vikas, primary, Montero Llopis, Paula, primary, Nieman, Linda T., primary, Song, Yuhui, primary, Xu, Katherine H., primary, Berger, Trisha R., primary, Kann, Michael C., primary, Leick, Mark B., primary, Silva, Harrison, primary, Salas-Benito, Diego, primary, Kienka, Tamina, primary, Grauwet, Korneel, primary, Armstrong, Todd D., primary, Zhang, Rui, primary, Zhu, Qingfeng, primary, Fu, Juan, primary, Schmidts, Andrea, primary, Korell, Felix, primary, Jan, Max, primary, Choi, Bryan D., primary, Liss, Andrew S., primary, Boland, Genevieve M., primary, Ting, David T., primary, Burkhart, Richard A., primary, Jenkins, Russell W., primary, Zheng, Lei, primary, Jaffee, Elizabeth M., primary, Zimmerman, Jacquelyn W., primary, and Maus, Marcela V., primary

Published
2024
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26. Stealth transgenes enable CAR-T cells to evade host immune responses

Author

Grauwet, Korneel, primary, Berger, Trisha, additional, Kann, Michael C, additional, Silva, Harrison, additional, Larson, Rebecca, additional, Leick, Mark B, additional, Bailey, Stefanie R, additional, Bouffard, Amanda A, additional, Millar, David, additional, Gallagher, Kathleen, additional, Turtle, Cameron J, additional, Frigault, Matthew J, additional, and Maus, Marcela V, additional

Published
2024
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27. Data from Mesothelin CAR T Cells Secreting Anti-FAP/Anti-CD3 Molecules Efficiently Target Pancreatic Adenocarcinoma and its Stroma

Author

Wehrli, Marc, primary, Guinn, Samantha, primary, Birocchi, Filippo, primary, Kuo, Adam, primary, Sun, Yi, primary, Larson, Rebecca C., primary, Almazan, Antonio J., primary, Scarfò, Irene, primary, Bouffard, Amanda A., primary, Bailey, Stefanie R., primary, Anekal, Praju Vikas, primary, Montero Llopis, Paula, primary, Nieman, Linda T., primary, Song, Yuhui, primary, Xu, Katherine H., primary, Berger, Trisha R., primary, Kann, Michael C., primary, Leick, Mark B., primary, Silva, Harrison, primary, Salas-Benito, Diego, primary, Kienka, Tamina, primary, Grauwet, Korneel, primary, Armstrong, Todd D., primary, Zhang, Rui, primary, Zhu, Qingfeng, primary, Fu, Juan, primary, Schmidts, Andrea, primary, Korell, Felix, primary, Jan, Max, primary, Choi, Bryan D., primary, Liss, Andrew S., primary, Boland, Genevieve M., primary, Ting, David T., primary, Burkhart, Richard A., primary, Jenkins, Russell W., primary, Zheng, Lei, primary, Jaffee, Elizabeth M., primary, Zimmerman, Jacquelyn W., primary, and Maus, Marcela V., primary

Published
2024
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28. Supplementary Methods 1 from Mesothelin CAR T Cells Secreting Anti-FAP/Anti-CD3 Molecules Efficiently Target Pancreatic Adenocarcinoma and its Stroma

Author

Wehrli, Marc, primary, Guinn, Samantha, primary, Birocchi, Filippo, primary, Kuo, Adam, primary, Sun, Yi, primary, Larson, Rebecca C., primary, Almazan, Antonio J., primary, Scarfò, Irene, primary, Bouffard, Amanda A., primary, Bailey, Stefanie R., primary, Anekal, Praju Vikas, primary, Montero Llopis, Paula, primary, Nieman, Linda T., primary, Song, Yuhui, primary, Xu, Katherine H., primary, Berger, Trisha R., primary, Kann, Michael C., primary, Leick, Mark B., primary, Silva, Harrison, primary, Salas-Benito, Diego, primary, Kienka, Tamina, primary, Grauwet, Korneel, primary, Armstrong, Todd D., primary, Zhang, Rui, primary, Zhu, Qingfeng, primary, Fu, Juan, primary, Schmidts, Andrea, primary, Korell, Felix, primary, Jan, Max, primary, Choi, Bryan D., primary, Liss, Andrew S., primary, Boland, Genevieve M., primary, Ting, David T., primary, Burkhart, Richard A., primary, Jenkins, Russell W., primary, Zheng, Lei, primary, Jaffee, Elizabeth M., primary, Zimmerman, Jacquelyn W., primary, and Maus, Marcela V., primary

Published
2024
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30. Anti-CD19 CAR T cells in combination with ibrutinib for the treatment of chronic lymphocytic leukemia

Author

Gill, Saar, Vides, Vanessa, Frey, Noelle V., Hexner, Elizabeth O., Metzger, Susan, O'Brien, Megan, Hwang, Wei-Ting, Brogdon, Jennifer L., Davis, Megan M., Fraietta, Joseph A., Gaymon, Avery L., Gladney, Whitney L., Lacey, Simon F., Lamontagne, Anne, Mato, Anthony R., Maus, Marcela V., Melenhorst, J. Joseph, Pequignot, Edward, Ruella, Marco, Shestov, Maksim, Byrd, John C., Schuster, Stephen J., Siegel, Donald L., Levine, Bruce L., June, Carl H., and Porter, David L.

Published
2022
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31. UCART19, a first-in-class allogeneic anti-CD19 chimeric antigen receptor T-cell therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukaemia (CALM): a phase 1, dose-escalation trial

Author

Benjamin, Reuben, Graham, Charlotte, Jozwik, Agnieszka, Yallop, Deborah, Bonganay, Laarni, Catt, Lorraine, Chappell, Jackie, Cheung, Gary, Chu, Vicky, Cuthill, Kirsty, Devereux, Steven, Dunlop, Alan, Ellard, Rose, Farzeneh, Farzin, Folarin, Najeem, Giemza, Elka, Kassam, Shireen, Kazmi, Majid, Kuhnl, Andrea, Lewis, Jen, Liskova, Maria, Mason, Alice, Metaxa, Victoria, Mufti, Ghulam, Munro, Helena, Pagliuca, Antonio, Patten, Piers, Potter, Victoria, Rice, Carmel, Saleem, Adeel, Sanderson, Robin, Stewart, Orla, Jabbour, Elias, Jain, Nitin, Jones, Emily, Kantarjian, Hagop, Kebriaei, Partow, Konopleva, Marina, McGee, Kara, Wierda, William, Brown, Jami, Casey, Keagan, Frigault, Matthew, Hock, Hanno, Mathews, Richard, Maus, Marcela, McKeown, Meaghan A, Spitzer, Thomas, Toncheva, Vesselina, Azoulay, Elie, Boissel, Nicolas, Caillat-Zucman, Sophie, Celli-Lebras, Karine, Clappier, Emmanuelle, Itzykson, Raphael, Larghero, Jérôme, Lengliné, Etienne, Madelaine, Isabelle, Meunier, Martine, Rabian, Florence, Raffoux, Emmanuel, Tremorin, Marie-Thérèse, Bonnin, Agnes, Brissot, Eolia, Daguenel-Nguyen, Anne, Dulery, Remy, Ledraa, Tounes, Malard, Florent, Mediavilla, Clemence, Mohty, Mohamad, Vekhoff, Anne, Teshima, Takanori, Kato, Koji, Maus, Marcela V, Frigault, Matthew J, Boucaud, Floriane, Balandraud, Svetlana, Gianella-Borradori, Athos, Binlich, Florence, Marchiq, Ibtissam, Dupouy, Sandra, Almena-Carrasco, Maria, Pannaux, Matthieu, and Fouliard, Sylvain

Published
2022
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35. CAR T cell killing requires the IFNγR pathway in solid but not liquid tumours

Author

Larson, Rebecca C., Kann, Michael C., Bailey, Stefanie R., Haradhvala, Nicholas J., Llopis, Paula Montero, Bouffard, Amanda A., Scarfó, Irene, Leick, Mark B., Grauwet, Korneel, Berger, Trisha R., Stewart, Kai, Anekal, Praju Vikas, Jan, Max, Joung, Julia, Schmidts, Andrea, Ouspenskaia, Tamara, Law, Travis, Regev, Aviv, Getz, Gad, and Maus, Marcela V.

Published
2022
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39. Safety and efficacy of tisagenlecleucel in primary CNS lymphoma: a phase 1/2 clinical trial

Author

Frigault, Matthew J., Dietrich, Jorg, Gallagher, Kathleen, Roschewski, Mark, Jordan, Justin T., Forst, Deborah, Plotkin, Scott R., Cook, Daniella, Casey, Keagan S., Lindell, Kevin A., Depinho, Gabriel D., Katsis, Katelin, Elder, Eva Lynn, Leick, Mark B., Choi, Bryan, Horick, Nora, Preffer, Frederic, Saylor, Meredith, McAfee, Steven, O'Donnell, Paul V., Spitzer, Thomas R., Dey, Bimalangshu, DeFilipp, Zachariah, El-Jawahri, Areej, Batchelor, Tracy T., Maus, Marcela V., and Chen, Yi-Bin

Published
2022
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40. Humoral and cellular immunogenicity of SARS-CoV-2 vaccines in chronic lymphocytic leukemia: a prospective cohort study

Author

Haydu, J. Erika, Maron, Jenny S., Redd, Robert A., Gallagher, Kathleen M.E., Fischinger, Stephanie, Barnes, Jeffrey A., Hochberg, Ephraim P., Johnson, P. Connor, Takvorian, R.W., Katsis, Katelin, Portman, Daneal, Ruiters, Jade, Sechio, Sidney, Devlin, Mary, Regan, Connor, Blumenthal, Kimberly G., Banerji, Aleena, Judd, Allen D., Scorsune, Krista J., McGree, Brianne M., Sherburne, Maryanne M., Lynch, Julia M., Weitzman, James I., Lei, Matthew, Kotton, Camille N., Dighe, Anand S., Maus, Marcela V., Alter, Galit, Abramson, Jeremy S., and Soumerai, Jacob D.

Published
2022
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43. Intraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma

Author

Choi, Bryan D., primary, Gerstner, Elizabeth R., additional, Frigault, Matthew J., additional, Leick, Mark B., additional, Mount, Christopher W., additional, Balaj, Leonora, additional, Nikiforow, Sarah, additional, Carter, Bob S., additional, Curry, William T., additional, Gallagher, Kathleen, additional, and Maus, Marcela V., additional

Published
2024
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44. Optimization of a flow cytometry test for routine monitoring of B cell maturation antigen targeted CAR in peripheral blood

Author

Lee, Won‐Ho, primary, Graham, Charlotte E., additional, Wiggin, Hadley R., additional, Nolan, Hannah K., additional, Graham, Kiana J., additional, Korell, Felix, additional, Leick, Mark B., additional, Barselau, Alexis L., additional, Emmanuel‐Alejandro, Estelle, additional, Trailor, Michael A., additional, Gildea, Juliane M., additional, Preffer, Frederic, additional, Frigault, Matthew J., additional, Maus, Marcela V., additional, and Gallagher, Kathleen M. E., additional

Published
2024
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48. Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs

Author

Lavin-Parsons, Kendall, Parry, Blair, Lilley, Brendan, Lodenstein, Carl, McKaig, Brenna, Charland, Nicole, Khanna, Hargun, Margolin, Justin, Gonye, Anna, Gushterova, Irena, Lasalle, Tom, Sharma, Nihaarika, Russo, Brian C., Rojas-Lopez, Maricarmen, Sade-Feldman, Moshe, Manakongtreecheep, Kasidet, Tantivit, Jessica, Fisher Thomas, Molly, Weingarten-Gabbay, Shira, Klaeger, Susan, Sarkizova, Siranush, Pearlman, Leah R., Chen, Da-Yuan, Gallagher, Kathleen M.E., Bauer, Matthew R., Taylor, Hannah B., Dunn, W. Augustine, Tarr, Christina, Sidney, John, Rachimi, Suzanna, Conway, Hasahn L., Katsis, Katelin, Wang, Yuntong, Leistritz-Edwards, Del, Durkin, Melissa R., Tomkins-Tinch, Christopher H., Finkel, Yaara, Nachshon, Aharon, Gentili, Matteo, Rivera, Keith D., Carulli, Isabel P., Chea, Vipheaviny A., Chandrashekar, Abishek, Bozkus, Cansu Cimen, Carrington, Mary, Bhardwaj, Nina, Barouch, Dan H., Sette, Alessandro, Maus, Marcela V., Rice, Charles M., Clauser, Karl R., Keskin, Derin B., Pregibon, Daniel C., Hacohen, Nir, Carr, Steven A., Abelin, Jennifer G., Saeed, Mohsan, and Sabeti, Pardis C.

Published
2021
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50. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma

Author

O'Rourke, Donald M, Nasrallah, MacLean P, Desai, Arati, Melenhorst, Jan J, Mansfield, Keith, Morrissette, Jennifer JD, Martinez-Lage, Maria, Brem, Steven, Maloney, Eileen, Shen, Angela, Isaacs, Randi, Mohan, Suyash, Plesa, Gabriela, Lacey, Simon F, Navenot, Jean-Marc, Zheng, Zhaohui, Levine, Bruce L, Okada, Hideho, June, Carl H, Brogdon, Jennifer L, and Maus, Marcela V

Subjects
Neurosciences, Immunization, Cancer, Rare Diseases, Brain Cancer, Biotechnology, Brain Disorders, Stem Cell Research - Nonembryonic - Human, Stem Cell Research, Clinical Research, Vaccine Related, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, Aged, Brain Neoplasms, Cell- and Tissue-Based Therapy, ErbB Receptors, Female, Glioblastoma, Humans, Immunohistochemistry, Immunotherapy, Adoptive, Male, Middle Aged, Neoplasm Recurrence, Local, Receptors, Antigen, T-Cell, Biological Sciences, Medical and Health Sciences
Abstract

We conducted a first-in-human study of intravenous delivery of a single dose of autologous T cells redirected to the epidermal growth factor receptor variant III (EGFRvIII) mutation by a chimeric antigen receptor (CAR). We report our findings on the first 10 recurrent glioblastoma (GBM) patients treated. We found that manufacturing and infusion of CAR-modified T cell (CART)-EGFRvIII cells are feasible and safe, without evidence of off-tumor toxicity or cytokine release syndrome. One patient has had residual stable disease for over 18 months of follow-up. All patients demonstrated detectable transient expansion of CART-EGFRvIII cells in peripheral blood. Seven patients had post-CART-EGFRvIII surgical intervention, which allowed for tissue-specific analysis of CART-EGFRvIII trafficking to the tumor, phenotyping of tumor-infiltrating T cells and the tumor microenvironment in situ, and analysis of post-therapy EGFRvIII target antigen expression. Imaging findings after CART immunotherapy were complex to interpret, further reinforcing the need for pathologic sampling in infused patients. We found trafficking of CART-EGFRvIII cells to regions of active GBM, with antigen decrease in five of these seven patients. In situ evaluation of the tumor environment demonstrated increased and robust expression of inhibitory molecules and infiltration by regulatory T cells after CART-EGFRvIII infusion, compared to pre-CART-EGFRvIII infusion tumor specimens. Our initial experience with CAR T cells in recurrent GBM suggests that although intravenous infusion results in on-target activity in the brain, overcoming the adaptive changes in the local tumor microenvironment and addressing the antigen heterogeneity may improve the efficacy of EGFRvIII-directed strategies in GBM.

Published
2017

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