{"id":"doi:10.1172/jci.insight.174027","kind":"article","title":"CD4 T cell-activating neoantigens enhance personalized cancer vaccine efficacy","authors":["Huff AL","Longway G","Mitchell JT","Andaloori L","Davis-Marcisak E","Chen F","Lyman MR","Wang R","Mathew J","Barrett B","Rahman S","Leatherman J","Yarchoan M","Azad NS","Yegnasubramanian S","Kagohara LT","Fertig EJ","Jaffee EM","Armstrong TD","Zaidi N"],"author_count":20,"year":2023,"published":"2023-12-08","venue":"JCI insight","cited_by":35,"doi":"10.1172/jci.insight.174027","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1172/jci.insight.174027","archive_url":"https://space-kitty.com/papers/doi:10.1172/jci.insight.174027","updated":null,"pmid":"38063199","pmcid":"PMC10795827","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC10795827/pdf","abstract":"Personalized cancer vaccines aim to activate and expand cytotoxic antitumor CD8+ T cells to recognize and kill tumor cells. However, the role of CD4+ T cell activation in the clinical benefit of these vaccines is not well defined. We previously established a personalized neoantigen vaccine (PancVAX) for the pancreatic cancer cell line Panc02, which activates tumor-specific CD8+ T cells but required combinatorial checkpoint modulators to achieve therapeutic efficacy. To determine the effects of neoantigen-specific CD4+ T cell activation, we generated a vaccine (PancVAX2) targeting both major histocompatibility complex class I- (MHCI-) and MHCII-specific neoantigens. Tumor-bearing mice vaccinated with PancVAX2 had significantly improved control of tumor growth and long-term survival benefit without concurrent administration of checkpoint inhibitors. PancVAX2 significantly enhanced priming and recruitment of neoantigen-specific CD8+ T cells into the tumor with lower PD-1 expression after reactivation compared with the CD8+ vaccine alone. Vaccine-induced neoantigen-specific Th1 CD4+ T cells in the tumor were associated with decreased Tregs. Consistent with this, PancVAX2 was associated with more proimmune myeloid-derived suppressor cells and M1-like macrophages in the tumor, demonstrating a less immunosuppressive tumor microenvironment. This study demonstrates the biological importance of prioritizing and including CD4+ T cell-specific neoantigens for personalized cancer vaccine modalities.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"CD4 T cell-activating neoantigens enhance personalized cancer vaccine efficacy\" by Huff AL, Longway G, Mitchell JT et al., https://doi.org/10.1172/jci.insight.174027, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"mrna-cancer-vaccines","name":"mRNA Therapeutics & Cancer Vaccines","domain_slug":"medicine"}],"cited_in_dossiers":[]}