Abstract 265: Robust anti-tumor effects of combined anti-CD4 depleting antibody and anti-PD-1/PD-L1 immune checkpoint antibody treatment in mice

Depletion of CD4+ cells in tumor-bearing mice has strong anti-tumor effects. However, the mechanisms underlying these effects and the therapeutic benefits of CD4+ cell depletion relative to other immunotherapies have not been fully evaluated. Here, we investigated the anti-tumor effects of an anti-CD4 depleting monoclonal antibody (mAb) as a monotherapy or in combination with immune checkpoint mAbs. In B16F10, Colon 26 or LLC subcutaneous tumor models, administration of the anti-CD4 mAb alone had strong anti-tumor effects that were superior to those elicited by CD25+ Treg depletion or other immune checkpoint mAbs, and which were completely reversed by CD8+ cell depletion. CD4+ cell depletion led to the proliferation of tumor-specific CD8+ T cells in the draining lymph node and increased infiltration of PD-1+CD8+ T cells into the tumor, with a shift towards type I immunity within the tumor. Combination treatment with the anti-CD4 mAb and immune checkpoint mAbs, particularly anti-PD-1 or anti-PD-L1 mAbs, synergistically suppressed tumor growth and greatly prolonged survival. To our knowledge, this work represents the first report of robust synergy between anti-CD4 and anti-PD-1 or anti-PD-L1 mAb therapies. Citation Format: Satoru Ito, Kouji Matsushima, Satoshi Ueha, Shoji Yokochi, Yoshiro Ishiwata, Kosuke Hachiga, Haru Ogiwara, Krishant Chand, Takumi Nakajima. Robust anti-tumor effects of combined anti-CD4 depleting antibody and anti-PD-1/PD-L1 immune checkpoint antibody treatment in mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 265. doi:10.1158/1538-7445.AM2015-265