Monoclonal antibodies (mAbs) can destroy tumors by recruiting effectors such as myeloid cells, or targeting immunomodulatory receptors to promote cytotoxic T cell responses. Here, we examined the therapeutic potential of combining a direct tumor-targeting mAb, anti-CD20, with an extended panel of immunomodulatory mAbs. Only the anti-CD27/CD20 combination provided cures. This was apparent in multiple lymphoma models, including huCD27 transgenic mice using the anti-huCD27, varlilumab. Detailed mechanistic analysis using single-cell RNA sequencing demonstrated that anti-CD27 stimulated CD8⁺ T and natural killer cells to release myeloid chemo-attractants and interferon gamma, to elicit myeloid infiltration and macrophage activation. This study demonstrates the therapeutic advantage of using an immunomodulatory mAb to regulate lymphoid cells, which then recruit and activate myeloid cells for enhanced killing of mAb-opsonized tumors.

中文翻译：

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CD27激动剂通过髓样募集增强了抗体靶向肿瘤的能力。

单克隆抗体（mAb）可以通过募集效应物（如髓样细胞）或靶向免疫调节受体来促进细胞毒性T细胞反应来破坏肿瘤。在这里，我们检查了将直接靶向肿瘤的单克隆抗体抗CD20与扩展的免疫调节单克隆抗体相结合的治疗潜力。仅抗CD27 / CD20组合可提供治疗。这在多种淋巴瘤模型中很明显，包括使用抗huCD27 varlilumab的huCD27转基因小鼠。使用单细胞RNA测序的详细机理分析表明，抗CD27刺激了CD8 ⁺T和自然杀伤细胞释放髓样化学吸引剂和干扰素γ，以引起髓样浸润和巨噬细胞活化。这项研究证明了使用免疫调节mAb调节淋巴样细胞的治疗优势，然后淋巴样细胞募集并激活髓样细胞以增强对mAb调理过的肿瘤的杀灭。