期刊
NATURE REVIEWS CLINICAL ONCOLOGY
卷 13, 期 1, 页码 25-40出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nrclinonc.2015.187
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资金
- National Institutes of Health [CA095152, CA138738, CA059350, CA008748]
- Juno Therapeutics
- William Lawrence Blanche Hughes Foundation
- Emerald Foundation
- Damon Runyon Clinical Investigator Award
- Annual Terry Fox Run for Cancer Research
- Kate's Team
- Mr William H. Goodwin and Mrs Alice Goodwin
- Commonwealth Cancer Foundation for Research
- Experimental Therapeutics Center of Memorial Sloan Kettering Cancer Center
- Geoffrey Beene Cancer Foundation
- Bayer
- BMS
- Celgene
- Incyte
- Janssen RD
- Sanofi
- Seattle Genetics
- Takeda Millenium
- John and Barbara Vogelstein Foundation
- Mortimer J. Lacher Foundation
- NATIONAL CANCER INSTITUTE [P01CA059350, K08CA095152, P30CA008748, R01CA138738] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR002384] Funding Source: NIH RePORTER
The success of the anti-CD20 monoclonal antibody rituximab in the treatment of lymphoid malignancies provided proof-of-principle for exploiting the immune system therapeutically. Since the FDA approval of rituximab in 1997, several novel strategies that harness the ability of T cells to target cancer cells have emerged. Reflecting on the promising clinical efficacy of these novel immunotherapy approaches, the FDA has recently granted 'breakthrough' designation to three novel treatments with distinct mechanisms. First, chimeric antigen receptor (CAR)-T-cell therapy is promising for the treatment of adult and paediatric relapsed and/or refractory acute lymphoblastic leukaemia (ALL). Second, blinatumomab, a bispecific T-cell engager (BiTE (R)) antibody, is now approved for the treatment of adults with Philadelphia-chromosomenegative relapsed and/or refractory B-precursor ALL. Finally, the monoclonal antibody nivolumab, which targets the PD-1 immune-checkpoint receptor with high affinity, is used for the treatment of Hodgkin lymphoma following treatment failure with autologous-stem-cell transplantation and brentuximab vedotin. Herein, we review the background and development of these three distinct immunotherapy platforms, address the scientific advances in understanding the mechanism of action of each therapy, and assess the current clinical knowledge of their efficacy and safety. We also discuss future strategies to improve these immunotherapies through enhanced engineering, biomarker selection, and mechanism-based combination regimens.
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