Combination immunotherapy with Interleukin-2 and CTLA-4 blockade decreases tumor growth and improves overall survival

Background Combination immunotherapy is quickly gaining attention in the field of cancer treatment. IL-2, a cytokine which activates T cells, and ipilimumab, a monoclonal antibody that blocks CTLA-4, are both approved as monotherapy for metastatic melanoma. To date, combination immu- notherapy with IL-2 and anti-CTLA-4 has not been adequately investigated. We hypothesized that that this combination may work synergistically owing to its dis- tinct but complementary mechanisms of T cell activation. mean tumor area with combination IL-2 and anti-CTLA- 4 was 2mm2, while in the anti-CTLA-4 only, IL-2 only, and placebo groups it was 14, 29, and 68 mm2, respec- tively (P<0.01 for all comparisons, except IL-2 only ver- sus anti-CTLA-4 only (not significant)). At day 30, the overall survival with combination IL-2 and anti-CTLA-4 was 50%, while with IL-2 only and anti-CTLA-4 only it was 10% and 20%, respectively (P<0.01 for all compari- sons). All animals treated in the placebo group suc- cumbed to their tumors by day 19. These findings were confirmed in a second experiment with similar results. Conclusions Combination immunotherapy with IL-2 activation and CTLA-4 blockade significantly decreases tumor growth and increases overall survival when compared to IL-2 or anti-CTLA-4 monotherapy or placebo. The role of CD8+ effector versus CD4+ regulatory T cells in the success of this immunotherapy is ongoing and will be included in our formal presentation. Ultimately, we aim to translate this work into a combination immunotherapy clinical trial.