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The evolution of checkpoint blockade as a cancer therapy: what's here, what's next?

Daniel Sanghoon Shin1, Antoni Ribas2

  • 1Department of Medicine, Division of Hematology-Oncology, University of California Los Angeles (UCLA), Los Angeles, CA, USA; Department of Molecular, Cellular and Integrative Physiology, UCLA, Los Angeles, CA, USA.

Current Opinion in Immunology
|January 27, 2015
PubMed

Insights

Cancer immunotherapy harnesses the immune system to fight tumors. Combining checkpoint inhibitors like anti-CTLA-4 and anti-PD-1 shows promise for melanoma and other cancers, with new targets emerging.

Area of Science:

  • Immunology
  • Oncology
  • Pharmacology

Background:

  • Cancer immunotherapy has revolutionized treatment since ipilimumab's approval in 2011.
  • Anti-PD-1 antibodies (pembrolizumab, nivolumab) are approved for melanoma and studied in various cancers.
  • Combining anti-CTLA-4 and anti-PD-1 therapies shows high response rates and manageable toxicity in advanced melanoma.

Purpose of the Study:

  • To review the current landscape of immune checkpoint inhibitors in cancer treatment.
  • To highlight emerging checkpoint targets like LAG-3 and TIM-3.
  • To discuss future directions in combination immunotherapies and biomarker discovery.

Main Methods:

  • Review of clinical data and preclinical studies on immune checkpoint inhibitors.
  • Analysis of combination therapy outcomes for advanced melanoma.
  • Exploration of novel checkpoint targets and therapeutic strategies.

Main Results:

  • Combination therapy of anti-CTLA-4 and anti-PD-1 antibodies yields impressive response rates in advanced melanoma.
  • Emerging checkpoint targets (LAG-3, TIM-3) show promising preclinical activity.
  • Investigational anti-PD-1/L1 antibodies are being explored across multiple cancer types.

Conclusions:

  • Immune checkpoint blockade is a cornerstone of modern cancer therapy.
  • Combination strategies and novel targets like LAG-3 and TIM-3 offer future therapeutic potential.
  • Defining biomarkers and optimizing combination regimens are crucial for advancing immunotherapy.

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