American Association for Cancer Research
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Supplementary Figure S4 from Rational Combination of Immunotherapies with Clinical Efficacy in Mice with Advanced Cancer

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posted on 2023-04-03, 23:00 authored by Ali Bransi, Oscar Camilo Salgado, Michal Beffinger, Karim Milo, Karina Silina, Hideo Yagita, Burkhard Becher, Alexander Knuth, Maries van den Broek

Administration of anti-CD40 + IL-2 complexes + IL-12Fc improves local and systemic tumor-specific immunity.

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ARTICLE ABSTRACT

In the context of cancer, naïve T cells are insufficiently primed and become progressively dysfunctional. Boosting antitumor responses by blocking PD-1 or CTLA-4 results in durable clinical responses only in a limited proportion of cancer patients, suggesting that other pathways must be targeted to improve clinical efficacy. Our preclinical study in TRAMP mice comparing 14 different immune interventions identified anti-CD40 + IL2/anti-IL2 complexes + IL12Fc as a uniquely efficacious treatment that prevents tolerance induction, promotes priming of sustained, protective tumor-specific CD8+ T cells, and cures late-stage cancer when given together with adoptively transferred tumor-specific T cells. We propose that improving signals 2 (costimulation) and 3 (cytokines) together with fresh tumor-specific, rather than boosting of dysfunctional preexisting memory, T cells represents a potent therapy for advanced cancer. Cancer Immunol Res; 3(11); 1279–88. ©2015 AACR.

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