Neoantigen-based cancer vaccination using chimeric RNA-loaded dendritic cell-derived extracellular vesicles

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Abstract

Cancer vaccines critically rely on the availability of targetable immunogenic cancer-specific neoepitopes. However, mutation-based immunogenic neoantigens are rare or even non-existent in subgroups of cancer types. To address this issue, we exploited a cancer-specific aberrant transcription-induced chimeric RNA, designated A-PaschiRNA, as a possible source of clinically relevant and targetable neoantigens. A-PaschiRNA encodes a recently discovered cancer-specific chimeric protein that comprises full-length astrotactin-2 (ASTN2) C-terminally fused in-frame to the antisense sequence of the 18th intron of pregnancy-associated plasma protein-A (PAPPA). We used extracellular vesicles (EVs) from A-PaschiRNA-transfected dendritic cells (DCs) to produce the cell-free anticancer vaccine DEXA-P. Treatment of immunocompetent cancer-bearing mice with DEXA-P inhibited tumour growth and prolonged animal survival. In summary, we demonstrate for the first time that cancer-specific transcription-induced chimeric RNAs can be exploited to produce a cell-free cancer vaccine that induces potent CD8+ T cell-mediated anticancer immunity. Our novel approach may be particularly useful for developing cancer vaccines to treat malignancies with low mutational burden or without mutation-based antigens. Moreover, this cell-free anticancer vaccine approach may offer several practical advantages over cell-based vaccines, such as ease of scalability and genetic modifiability as well as enhanced shelf life.

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APA

Xiong, X., Ke, X., Wang, L., Lin, Y., Wang, S., Yao, Z., … Zhang, H. (2022). Neoantigen-based cancer vaccination using chimeric RNA-loaded dendritic cell-derived extracellular vesicles. Journal of Extracellular Vesicles, 11(8). https://doi.org/10.1002/jev2.12243

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