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Combination Immunotherapy Shows Promise in Treating Prostate Cancer

Strategic Insights

— 1 min read

Researchers at the University of California have made significant progress in developing a new approach to treating prostate cancer, combining the blockade of CTLA4, a costimulatory molecule, with granulocyte macrophage colony-stimulating factor (GM-CSF)-based immunotherapies. This combination therapy has shown promising results in a phase I trial, inducing the expansion of activated, circulating CD25(+) CD69(+) CD8(+) T cells and antibody responses to tumor-associated antigens.

Key Takeaways:

  • The combination of CTLA4 blockade and GM-CSF-based immunotherapies has been shown to enhance antitumor efficacy in animal models and is being developed as a treatment for cancer patients.
  • 24 patients with metastatic, castration-resistant prostate cancer were treated in a phase I trial with sequential cohorts receiving increasing doses of ipilimumab, a fully human anti-CTLA4 antibody, and GM-CSF.
  • Of the six patients treated at the highest dose level, three had confirmed PSA declines of 50%, including one patient that had a partial response in visceral metastases.
  • Expansion of activated, circulating CD25(+) CD69(+) CD8(+) T cells occurred more frequently at higher doses of treatment and was greater in magnitude than was seen in patients who received the same doses of either ipilimumab or GM-CSF alone.
  • The combination therapy induced the expansion of T cells that are specific for known tumor-associated antigens from the endogenous immune repertoire.
  • The researchers concluded that this combination immunotherapy can induce the expansion of activated effector CD8 T cells and T cells specific for tumor-associated antigens.

Statistics:

  • 24 patients with metastatic, castration-resistant prostate cancer were treated in a phase I trial.
  • 6 patients were treated at the highest dose level of ipilimumab.
  • 3 patients had confirmed PSA declines of 50% at the highest dose level.
  • 1 patient had a partial response in visceral metastases at the highest dose level.
  • The expansion of activated, circulating CD25(+) CD69(+) CD8(+) T cells occurred more frequently at higher doses of treatment.

Sources:

  • L. Fong and colleagues, "Potentiating Endogenous Antitumor Immunity to Prostate Cancer through Combination Immunotherapy with CTLA4 Blockade and GM-CSF.," Cancer Research, vol. 69, no. 2, 2009, pp. 609-615, doi: 10.1158/0008-5472.CAN-08-2433.
  • University of California, Division of Hematology Oncology, San Francisco, CA 94143, USA.
  • American Association for Cancer Research, 615 Chestnut St., 17th Floor, Philadelphia, PA 19106-4404, USA.

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