Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy

SL Topalian, JM Taube, RA Anders… - Nature Reviews Cancer, 2016 - nature.com
Nature Reviews Cancer, 2016nature.com
With recent approvals for multiple therapeutic antibodies that block cytotoxic T lymphocyte
associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) in melanoma,
non-small-cell lung cancer and kidney cancer, and additional immune checkpoints being
targeted clinically, many questions still remain regarding the optimal use of drugs that block
these checkpoint pathways. Defining biomarkers that predict therapeutic effects and adverse
events is a crucial mandate, highlighted by recent approvals for two PDL1 diagnostic tests …
Abstract
With recent approvals for multiple therapeutic antibodies that block cytotoxic T lymphocyte associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) in melanoma, non-small-cell lung cancer and kidney cancer, and additional immune checkpoints being targeted clinically, many questions still remain regarding the optimal use of drugs that block these checkpoint pathways. Defining biomarkers that predict therapeutic effects and adverse events is a crucial mandate, highlighted by recent approvals for two PDL1 diagnostic tests. Here, we discuss biomarkers for anti-PD1 therapy based on immunological, genetic and virological criteria. The unique biology of the CTLA4 immune checkpoint, compared with PD1, requires a different approach to biomarker development. Mechanism-based insights from such studies may guide the design of synergistic treatment combinations based on immune checkpoint blockade.
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