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Toxicity patterns with immunomodulating antibodies and their combinations

John B A G Haanen1, Hans van Thienen1, Christian U Blank1

  • 1Division of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.

Seminars in Oncology
|May 13, 2015
PubMed

Insights

Immune checkpoint inhibitors like CTLA-4 and PD-1 block self-tolerance, enhancing anti-tumor immunity but causing autoimmune side effects. Immunosuppressive drugs effectively manage these immune-related adverse reactions.

Area of Science:

  • Immunology
  • Oncology
  • Pharmacology

Background:

  • Immune checkpoint molecules, including cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), LAG-3, and TIM-3, are crucial for maintaining peripheral tolerance and preventing autoimmunity.
  • Antibody-mediated blockade of these immune checkpoints unleashes potent anti-tumor immunity.

Purpose of the Study:

  • To review the toxicity patterns associated with immune checkpoint blockade therapies.
  • To describe adverse events resulting from both single-agent and combination immune checkpoint inhibitor treatments.

Main Methods:

  • Literature review of immune checkpoint blockade therapies.
  • Analysis of immune-related adverse reactions (irAEs) observed in clinical settings.

Main Results:

  • Immune checkpoint blockade, while effective against cancer, frequently leads to irAEs that mimic autoimmune diseases.
  • Combination therapies may present distinct or amplified toxicity profiles compared to single agents.

Conclusions:

  • Understanding toxicity patterns is essential for managing patients undergoing immune checkpoint blockade.
  • Prompt treatment with immunosuppressive drugs is effective in resolving irAEs and their associated symptoms.

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