A neoantigen-microbead platform for personalized T cell cancer vaccination

Jiang, L.; Akpinar, B.; Li, Y.; Sanaee, M.; Sanjaya, N. A.; Schmidt, K.; Woodbridge, A. F.; Nilsson, O. B.; Notari, L.; Kindler, C.; Rimke, I.; Thomas, O.; Kanatani, S.; Uhlen, P.; Widengren, J.; Graslund, T.; Wermeling, F.; Gronlund, H.

doi:10.1101/2025.11.21.689667

bioRxiv · 10.1101/2025.11.21.689667

A neoantigen-microbead platform for personalized T cell cancer vaccination

Jiang, L.·Akpinar, B.·Li, Y.·Sanaee, M.·Sanjaya, N. A.·Schmidt, K.·Woodbridge, A. F.·Nilsson, O. B.·Notari, L.·Kindler, C.·Rimke, I.·Thomas, O.·Kanatani, S.·Uhlen, P.·Widengren, J.·Graslund, T.·Wermeling, F.·Gronlund, H.

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Abstract

Colorectal cancer (CRC) is a leading cause of cancer mortality and is characterized by a high tumor mutational burden, making it responsive to immunotherapy. We developed a bioinformatic and manufacturing pipeline for personalized cancer vaccines and evaluated it in the MC38 colon adenocarcinoma mouse model. Thirty-six high-scoring neoantigens (NAGs) were identified by exome and transcriptome analysis, produced as six purified polypeptides, and coupled to paramagnetic beads. Intralymphatic vaccination of C57BL/6 mice with NAG beads induced robust NAG-specific T cell and antibody responses, resulting in significant inhibition of MC38 tumor growth. Treated tumors displayed increased necrosis and CD8+ T cell infiltration. Compared with soluble peptides, bead-coupled antigens elicited superior protection. Studies in T cell-deficient and antibody-depleted mice confirmed that both CD4+ and CD8+ T cells mediated the antitumor effect. These findings highlight the potential of NAG bead vaccination as an effective immunotherapy for CRC.

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Jiang, L., Akpinar, B., Li, Y., Sanaee, M., Sanjaya, N. A., Schmidt, K., Woodbridge, A. F., Nilsson, O. B., Notari, L., Kindler, C., Rimke, I., Thomas, O., Kanatani, S., Uhlen, P., Widengren, J., Graslund, T., Wermeling, F., Gronlund, H.. 2025-11-22. A neoantigen-microbead platform for personalized T cell cancer vaccination. https://doi.org/10.1101/2025.11.21.689667

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