Abstract B11: Low-dose HMGN1 synergistically enhances antitumor immunity in CD4 depleting antibody-treated mice

2018 
Anti-CD4 antibody treatment increases the number of and activates tumor-specific CD8 + T cells by depleting immunosuppressive cell populations (such as CD4 + Foxp3 + T cells), thus suppressing tumor growth in mice [Ueha et al, Cancer Immunol Res, 3:631 (2015)]. Co-administration of anti-CD4 antibody with other immune stimulators can further augments its anti-tumor efficacy. Here, we co-administered an alarmin, high mobility group nucleosome binding protein 1 (HMGN1), with an anti-CD4 antibody. In the Colon26 subcutaneous tumor model, anti-CD4 antibody with low-dose HMGN1 ( + migratory dendritic cells (mDCs) expressed higher level of co-stimulatory receptors (CD80 and CD86), and the number of CCR7 + mDCs and CD8 + CD137 + PD-1 + T cells further increased in the tumor. Collectively, these results suggest that low-dose HMGN1 may mobilize and activate the CCR7 + migratory DCs and tumor specific CD8 + T cells in the tumor. Combination therapy with low-dose HMGN1 and CD4 depleting antibody represents a new strategy to treat solid tumors. Citation Format: Chang-Yu Chen, Satoshi Ueha, Shoji Yokochi, Yoshiro Ishiwata, Haru Ogiwara, Shungo Deshimaru, Kouji Matsushima. Low-dose HMGN1 synergistically enhances antitumor immunity in CD4 depleting antibody-treated mice [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr B11.
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