Synergism between CTLA-4 and PD-(L)1 inhibition: the nivolumab-ipilimumab story

BJMO - 2020, issue Special, december 2020

J. Blokken PhD, PharmD, Tom Feys MBA, MSc, P. Coulie MD, PhD

In recent years, the approval of anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed cell death protein 1 (PD-1) antibodies have led to significant improvements in disease outcomes for various cancers. Despite their long-term durable efficacy, the responses to immune checkpoint blockade are limited to a minority of patients. In an attempt to overcome this, the combination of CTLA-4 and PD-1 inhibitors is gaining momentum as a rational approach to improve outcomes.1 This review describes the mechanism of action of both nivolumab and ipilimumab and discusses how the combined use of both drugs leads to potential synergism. The final part of the article assesses the extent to which this theoretical synergism is translated into a clinical benefit for cancer patients.

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