A neoantigen-microbead platform for personalized T cell cancer vaccination

Long Jiang; Birce Akpinar; Yue Li; Maryam Sanaee; Nathaniel A. Sanjaya; Karen Schmidt; Alejandro Fernandez-Woodbridge; Ola B. Nilsson; Luigi Notari; Csaba Kindler; Ingo Rimke; Olivia G. Thomas; Shigeaki Kanatani; Per Uhlén; Jerker Widengren; Torbjörn Gräslund; Fredrik Wermeling; Hans Grönlund

doi:10.1101/2025.11.21.689667

Cancer BiologybioRxivNov 21, 2025

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A neoantigen-microbead platform for personalized T cell cancer vaccination

Long Jiang iD, Birce Akpinar, Yue Li iD, Maryam Sanaee iD, Nathaniel A. Sanjaya iD, Karen Schmidt, Alejandro Fernandez-Woodbridge iD, Ola B. Nilsson iD, Luigi Notari, Csaba Kindler iD, Ingo Rimke, Olivia G. Thomas iD, Shigeaki Kanatani iD, Per Uhlén iD, Jerker Widengren iD, Torbjörn Gräslund iD, Fredrik Wermeling iD, Hans Grönlund iD

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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.