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New pathways in immune stimulation: targeting OX40

Carolina Alves Costa Silva1, Francesco Facchinetti2, Bertrand Routy3

  • 1Departement de la Recherche, Gustave Roussy Institute, Villejuif, France.

ESMO Open
|May 12, 2020
PubMed

Insights

Immune checkpoint blockers (ICB) show promise in cancer treatment but face resistance. Targeting the OX40 molecule offers a new strategy to enhance immune responses against tumors, potentially improving patient outcomes.

Area of Science:

  • Immunology
  • Oncology
  • Pharmacology

Background:

  • Immune checkpoint blockers (ICB) like anti-Programmed cell death 1 (PD-1)/Programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibodies have revolutionized cancer therapy.
  • Despite successes, primary and acquired resistance to ICB, along with immune-related toxicities, limit their efficacy.
  • Direct immune system stimulation presents a promising avenue for overcoming these limitations and improving cancer treatment.

Purpose of the Study:

  • To review the rationale behind targeting the co-stimulatory molecule OX40 (CD134) for cancer immunotherapy.
  • To highlight the potential of combining OX40-directed therapies with other anticancer agents.
  • To explore novel strategies for enhancing anti-tumor immune responses.

Main Methods:

  • Review of existing literature on immune checkpoint inhibitors and OX40 agonists.
  • Analysis of preliminary clinical trial data for OX40-targeting agents.
  • Exploration of combination strategies involving OX40 stimulation and other cancer treatments.

Main Results:

  • ICB combinations with chemotherapy or anti-angiogenic compounds yield significant results in various tumor types.
  • Early clinical trials investigating OX40 stimulation show encouraging preliminary outcomes.
  • OX40 targeting represents a next-generation approach in cancer immunotherapy.

Conclusions:

  • OX40 stimulation is a promising strategy to enhance anti-tumor immunity.
  • Combining OX40-directed therapies with existing anticancer agents may overcome resistance and improve durable responses.
  • Further research and clinical trials are warranted to fully realize the potential of OX40-based cancer therapies.
Keywords:
OX40OX40LT cellscancerimmunotherapy

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