Fucosyltransferase 4-derived peptide bioconjugates on carbon nanotubes enhance antitumor immunity in an ovarian cancer mouse model.

Ovarian cancer is characterized by a profoundly immunosuppressive tumor microenvironment, which has limited the clinical success of immunotherapy approaches. Antigen-based nanovaccines represent a promising strategy to enhance antitumor immunity by improving antigen delivery and immune activation. In this study, we evaluated carbon nanotubes (CNTs) bioconjugated with a peptide derived from tumor-associated antigen fucosyltransferase 4 (FUT4) as an immunomodulating platform in an immunocompetent ovarian cancer mouse model. FUT4 expression was confirmed in the ID8-Defb29/Vegf-a (ID8DVLuc) ovarian cancer model using flow cytometry and confocal microscopy. C57BL/6 mice were immunized with free peptide combined with a conventional adjuvant (PEP37 Adj), FUT4 peptide-conjugated CNTs (f-CNTs), or f-CNTs combined with adjuvant (f-CNTs Adj), and compared with nonimmunized controls. Immune profiling revealed increased leukocyte infiltration and enrichment of M1-like macrophages, dendritic cells, and CD8+ T cells, along with a reduction in regulatory T cells. f-CNT immunization also induced enhanced humoral responses, increased splenocyte proliferation upon ex vivo peptide restimulation, and increased ex vivo CD8+ T-cell-mediated cytotoxicity. Exploratory RNA sequencing of ascites-derived cells from f-CNT-immunized mice suggested the upregulation of genes associated with antigen processing and presentation, CD8+ T-cell activation, and Th1-type immune responses. Immunized mice exhibited reduced ascites accumulation, delayed disease progression, as assessed by bioluminescence imaging, and prolonged survival, with the most pronounced effects observed in the f-CNT group. Based on these findings, we propose that FUT4 peptide-conjugated CNTs function as an antigen-based nanoplatform that enhances antitumor immune responses in a murine ovarian cancer model. While additional studies are needed to further validate antigen specificity and therapeutic robustness, this work supports the potential of CNT-based nanocarriers as immune-modulating platforms for ovarian cancer immunotherapy.