多发性骨髓瘤（MM）是一种骨髓血液恶性肿瘤，在很大程度上仍然无法治愈。孤儿 G 蛋白偶联受体 GPRC5D 在浆细胞中独特表达，并在 MM 中高度表达，是免疫治疗的一个引人注目的候选者。在这项研究中，我们使用 5TGM1 MM 小鼠模型研究了编码小鼠 GPRC5D 的 DNA 疫苗和 PD-1 阻断剂组合在预防和治疗 MM 中的功效。单独的小鼠疫苗可有效预防骨髓瘤生长，但需要 PD-1 抗体来抑制已形成的 MM 肿瘤。接下来，我们评估了编码人 GPRC5D 的纳米质粒载体在几种小鼠同基因肿瘤模型中的预防和治疗效果。当 DNA 疫苗诱导人类 GPRC5D 特异性 T 细胞和抗体时，观察到了类似的肿瘤抑制结果。总而言之，这些发现强调了 GPRC5D 靶向 DNA 疫苗作为治疗和预防 MM 的多功能平台的潜力。© 2024。作者。

Multiple myeloma (MM), a hematological malignancy of the bone marrow, remains largely incurable. The orphan G protein-coupled receptor, GPRC5D, which is uniquely expressed in plasma cells and highly expressed in MM, is a compelling candidate for immunotherapy. In this study, we investigated the efficacy of a combination of DNA vaccine encoding mouse GPRC5D and PD-1 blockade in preventing and treating MM using the 5TGM1 murine model of MM. The mouse vaccine alone was effective in preventing myeloma growth but required PD-1 antibodies to inhibit established MM tumors. We next evaluated the prophylactic and therapeutic efficacy of a nanoplasmid vector encoding human GPRC5D in several murine syngeneic tumor models. Similar results for tumor inhibition were observed, as human GPRC5D-specific T cells and antibodies were induced by DNA vaccines. Taken together, these findings underscore the potential of GPRC5D-targeted DNA vaccines as versatile platforms for the treatment and prevention of MM.© 2024. The Author(s).