DNA vaccines against GPRC5D synergize with PD-1 blockade to treat multiple myeloma.

IF 6.9 1区 医学 Q1 IMMUNOLOGY NPJ Vaccines Pub Date : 2024-10-01 DOI:10.1038/s41541-024-00979-w
Praveen Neeli, Perry Ayn Mayson A Maza, Dafei Chai, Dan Zhao, Xen Ping Hoi, Keith Syson Chan, Ken H Young, Yong Li
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Abstract

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.

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针对 GPRC5D 的 DNA 疫苗与 PD-1 阻断疗法协同治疗多发性骨髓瘤。
多发性骨髓瘤(MM)是一种骨髓血液恶性肿瘤,在很大程度上仍无法治愈。孤儿G蛋白偶联受体GPRC5D在浆细胞中独特表达,在MM中高度表达,是一种令人信服的候选免疫疗法。在这项研究中,我们利用 5TGM1 小鼠 MM 模型研究了编码小鼠 GPRC5D 的 DNA 疫苗和 PD-1 阻断剂联合预防和治疗 MM 的疗效。单独使用小鼠疫苗可有效预防骨髓瘤生长,但需要 PD-1 抗体才能抑制已形成的 MM 肿瘤。接下来,我们评估了编码人类 GPRC5D 的纳米质粒载体在几种小鼠合成肿瘤模型中的预防和治疗效果。由于 DNA 疫苗诱导了人类 GPRC5D 特异性 T 细胞和抗体,因此也观察到了类似的肿瘤抑制结果。综上所述,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。
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来源期刊
NPJ Vaccines
NPJ Vaccines Immunology and Microbiology-Immunology
CiteScore
11.90
自引率
4.30%
发文量
146
审稿时长
11 weeks
期刊介绍: Online-only and open access, npj Vaccines is dedicated to highlighting the most important scientific advances in vaccine research and development.
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