Bispecific Antibodies to PD-1 and CTLA4: Doubling Down on T Cells to Decouple Efficacy from Toxicity
- PMID: 33947716
- DOI: 10.1158/2159-8290.CD-21-0257
Bispecific Antibodies to PD-1 and CTLA4: Doubling Down on T Cells to Decouple Efficacy from Toxicity
Abstract
Although combination anti-PD-1 and anti-CTLA4 mAbs have revolutionized outcomes for many cancers, their utility has been limited due to significant immune-related toxicities and the emergence of resistance. In this issue of Cancer Discovery, Dovedi and colleagues describe the development and preclinical testing of MEDI5752, a bispecific anti-PD-1/CTLA4 antibody designed to optimize therapeutic response by maximizing CTLA4 blockade on antigen-experienced T cells, thereby increasing efficacy and potentially minimizing toxicity.See related article by Dovedi et al., p. 1100.
©2021 American Association for Cancer Research.
Comment on
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Design and Efficacy of a Monovalent Bispecific PD-1/CTLA4 Antibody That Enhances CTLA4 Blockade on PD-1+ Activated T Cells.Cancer Discov. 2021 May;11(5):1100-1117. doi: 10.1158/2159-8290.CD-20-1445. Epub 2021 Jan 8. Cancer Discov. 2021. PMID: 33419761
References
-
- Larkin J, Chiarion-Sileni V, Gonzalez R, Grob J-J, Rutkowski P, Lao CD, et al. Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2019;381:1535–46.
-
- Hellmann MD, Paz-Ares L, Bernabe Caro R, Zurawski B, Kim SW, Carcereny Costa E, et al. Nivolumab plus ipilimumab in advanced non-small-cell lung cancer. N Engl J Med. 2019;381:2020–31.
-
- Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378:1277–90.
-
- Tawbi HA, Forsyth PA, Algazi A, Hamid O, Hodi FS, Moschos SJ, et al. Combined nivolumab and ipilimumab in melanoma metastatic to the brain. N Engl J Med. 2018;379:722–30.
-
- Ascierto PA, Del Vecchio M, Robert C, Mackiewicz A, Chiarion-Sileni V, Arance A, et al. Ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with unresectable or metastatic melanoma: a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2017;18:611–22.
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