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Professional Statement
Dr. Brenner's primary research interest is the use of gene transfer to augment the immune response to human tumors, using vaccines and adoptive transfer of genetically modified T cells.
In neuroblastoma, Dr. Brenner and co-investigators have shown that T cells expressing a chimeric antigen receptor (CAR) for a surface marker (GD2) on neuroblastoma cells can produce tumor responses in more than half the patients with refractory or relapsed disease leading to complete remission in 3/11 patients. His Center is also studying the benefits of T cells modified with CARs directed to other tumor antigens on hematological malignancies and solid tumors including Hodgkin Disease and Glioblastoma multiforme and initial clinical results are promising. Efforts are being made to further increase the effectiveness of these CAR-T cells by incorporating genes that enhance T cell growth and survival and that render the T cells resistant to the inhibitory effects of many human tumors.
To enhance the safety of genetically modified T cells, Dr. Brenner and colleagues have implemented an inducible caspase system that will rapidly cause apoptosis of T cells within minutes of administration of a small molecule dimerizing drug, allowing adverse effects from the T cells to be reversed. Initial clinical trials showed significant activity, and the approach is now being broadened to other novel T cell therapeutics.
Dr. Brenner’s group combines these adoptive transfer strategies with immunization against the tumors to produce synergistic benefits and clinical studies in chronic lymphocytic leukemia have recently begun.
Finally, in collaboration with the laboratories of Drs. Rooney, Heslop and Bollard, Dr. Brenner is continuing to study the use of gene modified cytotoxic T lymphocytes to prevent and treat the Epstein Barr virus associated malignancies, immunoblastic lymphoma, Hodgkin disease, and nasopharyngeal cancer (NPC). By transducing dendritic cells with EBV antigens, we are able to generate potent immune responses against the weak EBV latency antigens expressed in Hodgkin disease and NPC. Studies in 23 patients with relapsed or refractory EBV-positive Hodgkin and Non-Hodgkin lymphoma patients have produced complete responses in more than half. The potential to increase the effectiveness of the T-cells in vivo using monoclonal antibodies directed to immunological checkpoints is now being evaluated in clinical trials.
Dr. Brenner's primary research interest is the use of gene transfer to augment the immune response to human tumors, using vaccines and adoptive transfer of genetically modified T cells.
In neuroblastoma, Dr. Brenner and co-investigators have shown that T cells expressing a chimeric antigen receptor (CAR) for a surface marker (GD2) on neuroblastoma cells can produce tumor responses in more than half the patients with refractory or relapsed disease leading to complete remission in 3/11 patients. His Center is also studying the benefits of T cells modified with CARs directed to other tumor antigens on hematological malignancies and solid tumors including Hodgkin Disease and Glioblastoma multiforme and initial clinical results are promising. Efforts are being made to further increase the effectiveness of these CAR-T cells by incorporating genes that enhance T cell growth and survival and that render the T cells resistant to the inhibitory effects of many human tumors.
To enhance the safety of genetically modified T cells, Dr. Brenner and colleagues have implemented an inducible caspase system that will rapidly cause apoptosis of T cells within minutes of administration of a small molecule dimerizing drug, allowing adverse effects from the T cells to be reversed. Initial clinical trials showed significant activity, and the approach is now being broadened to other novel T cell therapeutics.
Dr. Brenner’s group combines these adoptive transfer strategies with immunization against the tumors to produce synergistic benefits and clinical studies in chronic lymphocytic leukemia have recently begun.
Finally, in collaboration with the laboratories of Drs. Rooney, Heslop and Bollard, Dr. Brenner is continuing to study the use of gene modified cytotoxic T lymphocytes to prevent and treat the Epstein Barr virus associated malignancies, immunoblastic lymphoma, Hodgkin disease, and nasopharyngeal cancer (NPC). By transducing dendritic cells with EBV antigens, we are able to generate potent immune responses against the weak EBV latency antigens expressed in Hodgkin disease and NPC. Studies in 23 patients with relapsed or refractory EBV-positive Hodgkin and Non-Hodgkin lymphoma patients have produced complete responses in more than half. The potential to increase the effectiveness of the T-cells in vivo using monoclonal antibodies directed to immunological checkpoints is now being evaluated in clinical trials.
研究兴趣
论文共 1045 篇作者统计合作学者相似作者
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Bloodno. 13 (2024): 1231-1241
David Steffin,Nisha Ghatwai,Antonino Montalbano,Purva Rathi,Amy N Courtney, Azlann B Arnett,Julien Fleurence,Ramy Sweidan, Thao Wang, Huimin Zhang,Prakash Masand,John M Maris, Daniel Martinez,Jennifer Pogoriler,Navin Varadarajan,Sachin G Thakkar,Deborah Lyon,Natasha Lapteva,Zhuyong Mei,Kalyani Patel,Dolores Lopez-Terrada,Carlos Ramos,Premal Lulla,Tannaz Armaghany,Bambi J Grilley,Gianpietro Dotti,Leonid S Metelitsa,Helen E Heslop,Malcolm K Brenner,Pavel Sumazin,Andras Heczey
Research square (2024)
Frank Y. Lin,Austin Stuckert,Candise Tat,Mark White,Lucia Ruggieri,Huimin Zhang,Birju Mehta,Natalia Lapteva,Zhuyong Mei,Angela Major,Sachin Thakkar,Thomas Shum,Kathan Parikh,Meng-Fen Wu,Holly B. Lindsay,Lauren Scherer,Meghan Shekar,Patricia Baxter,Tao Wang,Bambi Grilley, Karen Moeller,John Hicks,Angshumoy Roy,Jamie Anastas,Fatema Malbari,Guillermo Aldave,Murali Chintagumpala,Susan Blaney,D. Williams Parsons,Malcolm K. Brenner,Helen E. Heslop,Cliona M. Rooney,Bilal Omer
JOURNAL OF CLINICAL ONCOLOGYno. 23 (2024)
Benjamin L. Musher,Eric K. Rowinsky,Brandon G. Smaglo,Wasif Abidi,Mohamed Othman,Kalpesh Patel,Salmaan Jawaid,James Jing,Amanda Brisco, Ann M. Leen,Mengfen Wu,Linda C. Sandin,Jessica Wenthe, Emma Eriksson,Gustav J. Ullenhag,Bambi Grilley,Justyna Leja-Jarblad,Susan G. Hilsenbeck,Malcolm K. Brenner,Angelica S. Loskog
LANCET ONCOLOGYno. 4 (2024): 488-500
Transplantation and Cellular Therapyno. 2 (2024): S41-S42
Royce Ma, Mae Woods, Phillip Burkhardt, Noah Crooks, Dayenne G. van Leeuwen, Daniil Shmidt,Jacob Couturier, Alexandre Chaumette, Divya Popat,LaQuisa C. Hill,Rayne H. Rouce,Sachin Thakkar, Aaron F. Orozco,Alexandre F. Carisey,Malcolm K. Brenner,Maksim Mamonkin
Cell Reports Medicineno. 7 (2024): 101628
LaQuisa C. Hill,Rayne H. Rouce,Mengfen J. Wu, Tao Wang, Royce Ma,Huimin Zhang,Birju Mehta,Natalia Lapteva,Zhuyong Mei,Tyler S. Smith,Lina Yang,Madhuwanti Srinivasan, Phillip M. Burkhardt,Carlos A. Ramos,Premal Lulla, Martha Arredondo,Bambi Grilley,Helen E. Heslop,Malcolm K. Brenner,Maksim Mamonkin
BLOODno. 13 (2024)
Engineering Psychology and Cognitive Ergonomics Lecture Notes in Computer Sciencepp.3-13, (2024)
Cancer Researchno. 17_Supplement_2 (2024)
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作者统计
#Papers: 1046
#Citation: 56747
H-Index: 116
G-Index: 221
Sociability: 8
Diversity: 0
Activity: 4
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