Data from S-531011, a novel anti-human CCR8 antibody, induces potent anti-tumor responses through depletion of tumor-infiltrating CCR8-expressing regulatory T cells

• DOI: 10.1158/1535-7163.c.6784852.v3
• Publication Date: 2024-09-16T13:33:59Z
• Authors: Yoji Nagira; Morio Nagira; Ryohei Nagai; Wataru Nogami; Michinari Hirata; Azumi Ueyama; Tetsuya Yoshida; Mai Yoshikawa; Satomi Shinonome; Hiroshi Yoshida; Miya Haruna; Hiroto Miwa; Natsumi Chatani; Naganari Ohkura; Hisashi Wada; Hidekazu Tanaka

<div>Abstract<p>While regulatory T cells (Tregs) are inhibitory immune that essential for maintaining homeostasis, Tregs infiltrate tumor tissue promote growth by suppressing anti-tumor immunity. Selective reduction of tumor-infiltrating is therefore expected to activate immunity without affecting homeostasis. We previously reported selective Treg depletion targeted a C-C motif chemokine receptor 8 (CCR8) resulted in induction strong any obvious autoimmunity mouse models. Thus, herein, we developed novel humanized anti-CCR8 monoclonal antibody, S-531011, aimed as cancer immunotherapy strategy patients with cancer. S-531011 exclusively recognized human CCR8 among all receptors and showed potent antibody-dependent cell-mediated cytotoxicity activity toward CCR8+ neutralization against CCR8-mediated signaling. observed reduced induced tumor-bearing human-CCR8 knock-in model. Moreover, combination therapy anti-mouse programmed cell death 1 (PD-1) antibody strongly suppressed compared anti-PD-1 alone no observable adverse effects. also depleted Tregs, but not derived from peripheral blood mononuclear cells. These results suggest promising drug inducing severe side effects the clinical setting.</p></div>