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A Multivalent Personalized Vaccine Orchestrating Two-Signal Activation Rebuilds the Bridge Between Innate and
Xiaorong Kou1, Tao He1, Miaomiao Zhang1
1Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China.
Abstract:
Personalized vaccines capable of circumventing tumor heterogeneity have exhibited compelling prospects. However, their therapeutic benefit is greatly hindered by the limited antigen repertoire and poor response of CD8+ T-cell immunity. Here, a double-signal coregulated cross-linking hydrogel-based vaccine (Bridge-Vax) is engineered to rebuild the bridge between innate and adaptive immunity for activating CD8+ T-cells against full repertoire of tumor antigens. Mechanistically, unlike prominent CD4+ T-cell responses in most cases, administration of Bridge-Vax encapsulated with granulocyte-macrophage colony-stimulating factor concentrates a wave of dendritic cells (DCs), which further promotes DCs activation with costimulatory signal by the self-adjuvanted nature of polysaccharide hydrogel. Simultaneously, synergy with the increased MHC-I epitopes by codelivered simvastatin for cross-presentation enhancement, Bridge-Vax endows DCs with necessary two signals for orchestrating CD8+ T-cell activation. Bridge-Vax elicits potent antigen-specific CD8+ T-cell responses in vivo, which not only shows efficacy in B16-OVA model but confers specific immunological memory to protect against tumor rechallenge. Moreover, personalized multivalent Bridge-Vax tailored by leveraging autologous tumor cell membranes as antigens inhibits postsurgical B16F10 tumor recurrence. Hence, this work provides a facile strategy to rebuild the bridge between innate and adaptive immunity for inducing potent CD8+ T-cell immunity and would be a powerful tool for personalized cancer immunotherapy.
Insights
Bridge-Vax, a novel hydrogel vaccine, enhances CD8+ T-cell immunity against diverse tumor antigens. This approach overcomes limitations in current cancer vaccines, offering potent anti-tumor responses and immunological memory for personalized immunotherapy.
Area of Science:
- Biotechnology
- Immunology
- Materials Science
Background:
- Personalized vaccines show promise against tumor heterogeneity but face challenges with limited antigens and weak CD8+ T-cell responses.
- Current strategies often fail to elicit robust and comprehensive anti-tumor immunity, hindering therapeutic efficacy.
Purpose of the Study:
- To engineer a novel hydrogel-based vaccine (Bridge-Vax) that bridges innate and adaptive immunity to activate CD8+ T-cells against a full spectrum of tumor antigens.
- To enhance dendritic cell (DC) activation and antigen cross-presentation for potent CD8+ T-cell responses.
Main Methods:
- Development of a double-signal coregulated cross-linking hydrogel vaccine (Bridge-Vax) incorporating granulocyte-macrophage colony-stimulating factor and simvastatin.
- Utilizing autologous tumor cell membranes as antigens for personalized vaccine formulation.
- Evaluating vaccine efficacy in B16-OVA and B16F10 tumor models in vivo.
Main Results:
- Bridge-Vax effectively concentrates and activates dendritic cells (DCs), promoting T-cell activation through costimulatory signals and enhanced MHC-I cross-presentation.
- The vaccine elicits potent antigen-specific CD8+ T-cell responses, demonstrating efficacy in reducing tumor growth and establishing long-term immunological memory.
- Personalized multivalent Bridge-Vax formulations inhibited postsurgical tumor recurrence in a B16F10 model.
Conclusions:
- Bridge-Vax represents a facile strategy to rebuild the innate and adaptive immunity bridge, inducing potent CD8+ T-cell immunity.
- This platform offers a powerful tool for personalized cancer immunotherapy, addressing limitations of current vaccine approaches.
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