Seishima Noriko, Becker William, Olkhanud Purevdorj B, Maeng Hoyoung M, Lopez-Lago Miguel A, Williams William V, Berzofsky Jay A
Vaccine Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
BriaCell Therapeutics Corp., Philadelphia, Pennsylvania, USA.
JCI Insight. 2025 Jul 15;10(16). doi: 10.1172/jci.insight.189024. eCollection 2025 Aug 22.
We assessed the therapeutic efficacy of a semiallogeneic dendritic cell (DC) vaccine in comparison to a syngeneic one for suppression of B16-F10 and TC-1 tumors. Syngeneic bone marrow-derived DCs (BMDCs) were generated from C57BL/6J mice and semiallogeneic BMDCs with a mutation in either MHC class I or II were generated from B6.C-H2-Kbm1/ByJ or B6(C)-H2-Ab1bm12/KhEgJ mice, respectively. We demonstrated in vivo and in vitro that the MHC class II semiallogeneic BMDC vaccine had superior efficacy over the syngeneic and the MHC class I semiallogeneic BMDC vaccine, providing allogeneic CD4+ T cell help to enhance the antitumor CD8+ T cell response through allogeneic stimulation by the mutant MHC class II molecules. We discovered that this help was induced only at an early stage of tumor growth and at a later stage of tumor growth; combining our BMDC vaccine with Treg depletion enhanced tumor suppression. We demonstrated the improved efficacy of a semiallogeneic BMDC vaccine that kept tumor-peptide presentation intact on syngeneic MHC class I molecules so that mutant MHC class II could provide allogeneic help. This strategy should enable promising new DC-based cancer immunotherapies, offering an alternative to autologous DC vaccines by incorporating allogenicity as an adjuvant.
我们评估了半同种异体树突状细胞（DC）疫苗与同种基因DC疫苗相比对B16-F10和TC-1肿瘤的抑制治疗效果。同种基因骨髓来源的DC（BMDC）由C57BL/6J小鼠产生，而具有MHC I类或II类突变的半同种异体BMDC分别由B6.C-H2-Kbm1/ByJ或B6(C)-H2-Ab1bm12/KhEgJ小鼠产生。我们在体内和体外均证明，MHC II类半同种异体BMDC疫苗比同种基因和MHC I类半同种异体BMDC疫苗具有更高的疗效，通过突变的MHC II类分子的同种异体刺激提供同种异体CD4+ T细胞帮助，以增强抗肿瘤CD8+ T细胞反应。我们发现这种帮助仅在肿瘤生长的早期和晚期诱导；将我们的BMDC疫苗与调节性T细胞耗竭相结合可增强肿瘤抑制作用。我们证明了一种半同种异体BMDC疫苗的疗效得到改善，该疫苗在同种基因MHC I类分子上保持肿瘤肽呈递完整，从而使突变的MHC II类能够提供同种异体帮助。这种策略应能实现有前景的基于DC的新型癌症免疫疗法，通过将同种异体性作为佐剂纳入，为自体DC疫苗提供一种替代方案。
