Abstract
Therapeutic cancer vaccines (TCVs) remain limited in their capacity to elicit robust CD8⁺ cytolytic T lymphocyte responses. An effective cancer vaccine adjuvant should promote expansion of antigen-specific T cells through cross-presentation by type 1 conventional dendritic cells (cDC1s). For anti-PD-1 immune checkpoint inhibitor therapy, being frequently combined with cancer vaccines, requires an expanded pool of precursor-exhausted CD8⁺ T (Tpex) cells. Here, we report Flt3L-FlaB (FB), a hybrid adjuvant that integrates FMS-like tyrosine kinase 3 ligand (Flt3L) with the TLR5 agonist flagellin B (FlaB). FB significantly expanded and activated cDC1s, accompanied by increased CD8⁺ T cells with stem-like memory (Tscm) and Tpex phenotypes in tumors and draining lymph nodes. FB-adjuvanted TCVs, combined with anti-PD-1 therapy, achieved potentiated tumor suppression and provided durable protection against metastasis and high-dose tumor rechallenge. These results establish FB as a potent TCV adjuvant with strong translational potential, particularly the combination with anti-PD-1 immune checkpoint inhibitors.
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Sequence data for the engineered constructs are provided in Supplementary Table 5. All other data are included in the manuscript or are available from the corresponding authors upon reasonable request.
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Acknowledgements
The authors thank Dr. Sung-Woo Lee and Dr. Thanh Quang Tran for their valuable discussions. The authors also thank Min-Ju Ryu and Sun-Mi An for administrative assistance; Myeung Suk Kim for mice breeding and care; Seol Hee Hong and Yun Suhk Lee for assistance with animal experiments. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) 2020R1A5A2031185 (J.H.R), The National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) 2019R1A5A2027521 (S.E.L), The National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) RS-2025-00553055 (S.E.L) and The Korea Ministry of Food and Drug Safety grant 22213MFDS421 (S.E.L). Figures 1A, 2A, 3A, 5A, 6B, 7A, Supplementary Figs. 4, 5, 6, and 13 were generated by the authors using BioRender under an academic license.
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Conceptualization: G.C.D., S.E.L., J.H.R. Methodology: G.C.D., V.L., P.P., C.Y.S. Investigation and visualization: G.C.D., S.E.L., J.H.R. Supervision: S.E.L., J.H.R. Writing: G.C.D., S.E.L., J.H.R. Final approval of the version to be published: G.C.D., V.L., P.P., C.Y.S., S.E.L., J.H.R.
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Dang, G.C., Loeurng, V., Pa, P. et al. Antigen cross-presentation potentiating cancer vaccine adjuvant for T cell expansion and synergy with anti-PD-1. npj Vaccines (2026). https://doi.org/10.1038/s41541-026-01376-1
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DOI: https://doi.org/10.1038/s41541-026-01376-1
