Systemically administered extremely low HMGN1 with anti-CD4 depleting antibody exerts synergistic anti-tumor effects

Recently there has been growing interest in the immunomodulatory effects of endogenous danger signals known as alarmins. In this study, we explore a new combination therapy of anti-CD4 depleting antibody with an alarmin, high mobility group nucleosome binding protein 1 (HMGN1). Extremely low dose of HMGN1 with anti-CD4 depleting antibody exerted robust anti-tumor effects in Colon26 subtaneous murine model. To understand transcriptomic differences of CD8+ T cells in the tumor-bearing mice after treated with anti-CD4 depleting antibody or combination therapy of HMGN1 with anti-CD4 depleting antibody, we performed CD8 T cell transcriptome analysis using 3'SAGE-seq and Ion Proton sequencer. Overall design: CD8+ T cells were purified from single cell suspension of each implanted mouse tumor by lineage sorting (CD45-CD11b-B220-CD49b-Ter119-CD4-CD8+) through FACSAria. CD8 T cell transcriptome analysis were generated by 3'SAGE-seq using Ion Proton sequencer.

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Chen CY, Ueha S, Ishiwata Y, Yokochi S, Yang, Oppenheim JJ, Ogiwara H, Shichino S, Deshimaru S, Shand FHW, Shibayama S, Matsushima K