A novel whole cancer cell vaccine based on modified β-glucan elicits robust anti-tumor immunity

TL;DR

A new cancer vaccine using modified β-glucan boosts immune responses and improves survival in multiple cancer models.

Contribution

A novel conjugate adjuvant (G-PL) is developed to enhance whole-cell cancer vaccines.

Findings

G-PL adheres to cell membranes without toxicity and enhances dendritic cell activity.

ICC@G-PL activates immune responses and improves survival in glioblastoma, colon cancer, and melanoma models.

The vaccine increases anti-tumor immune cells and reprograms the tumor microenvironment.

Abstract

Background: Although autologous whole tumour cells provide broad-spectrum antigens for personalised cancer vaccines, their weak immunogenicity necessitates adjuvant co-delivery systems.

Methods: We developed a conjugate adjuvant (G-PL) by coupling modified yeast β-glucan with poly-D-lysine. Electron microscopy confirmed its binding to GL261 cell membranes. The adjuvant-cell complex (ICC@G-PL) was constructed by coating irradiated tumour cells with G-PL. We evaluated the recruitment/activation of dendritic cells (DCs), lymph node priming, tumour-specific immunity, and therapeutic efficacy in glioblastoma, colon cancer, and melanoma models. Dectin-1-mediated Th17 induction was analysed via Western blotting and flow cytometry.

Results: G-PL (≤ 500 μg/mL) rapidly adhered to cell membranes without cytotoxicity. In vitro, it enhanced DC uptake of tumour components, maturation, and non-pathogenic Th17 differentiation. In vivo, ICC@G-PL recruited DCs at injection sites, activated draining lymph nodes, and elevated plasma levels of IL-12, TNF-α, and IFN-γ. The vaccine prolonged survival in both therapeutic and preventive models, increasing intratumoral CD8+/CD4+ T cell ratios, M1 macrophages, and neutrophils. Dectin-1 downregulation in DCs correlated with Th17-driven anti-tumour responses.

Conclusions: G-PL, a novel β-glucan-based adjuvant, enables rapid construction of autologous whole-cell vaccines. This strategy enhances tumour-specific immunity and reprogrammes the tumour microenvironment, offering a universal platform for personalised cancer immunotherapy.

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