A facile approach to enhance antigen response for personalized cancer vaccination

Abstract

Existing strategies to enhance peptide immunogenicity for cancer vaccination generally require direct peptide alteration, which, beyond practical issues, may impact peptide presentation and result in vaccine variability. Here, we report a simple adsorption approach using polyethyleneimine (PEI) in a mesoporous silica microrod (MSR) vaccine to enhance antigen immunogenicity. The MSR–PEI vaccine significantly enhanced host dendritic cell activation and T-cell response over the existing MSR vaccine and bolus vaccine formulations. Impressively, a single injection of the MSR–PEI vaccine using an E7 peptide completely eradicated large, established TC-1 tumours in about 80% of mice and generated immunological memory. When immunized with a pool of B16F10 or CT26 neoantigens, the MSR–PEI vaccine eradicated established lung metastases, controlled tumour growth and synergized with anti-CTLA4 therapy. Our findings from three independent tumour models suggest that the MSR-PEI vaccine approach may serve as a facile and powerful multi-antigen platform to enable robust personalized cancer vaccination.

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Fig. 1: PEI can be rapidly incorporated onto MSRs and leads to murine and human DC activation.
Fig. 2: MSR–PEI vaccine enhances DC activation and trafficking in situ.
Fig. 3: MSR–PEI vaccine enhances CD8 cytotoxic T-cell response against OVA.
Fig. 4: MSR–PEI vaccine enhances CD8 cytotoxic T-cell response against E7 and regresses established tumours.
Fig. 5: MSR–PEI vaccine enhances melanoma TIL effector function and induces tumour control and synergy with anti-CTLA4 therapy using combined B16 neoantigens.

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Acknowledgements

The authors would like to thank C. J. Wu (Dana Farber Cancer Institute) for providing the human neoantigen peptides. We are also grateful to G. Dranoff, C. S. Verbeke, G. J. Xu and A. S. Cheung for their helpful discussions and feedback on the manuscript. This work was supported by the National Institutes of Health (NIH) R01EB015498 and R01EB023287, the Melanoma Research Alliance Foundation, the National Science Foundation (NSF) Graduate Research Fellowship Program (AWL) and the Wyss Institute for Biologically Inspired Engineering.

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A.W.L. and D.J.M. conceived the study, designed the experiments and wrote the manuscript, A.W.L., M.C.S., S.B., Y.C., A.G., A.G.S., J.C.W., M.O.D. and T-Y.S. carried out the experiments. S.B. and K.W.W. designed and carried out the TIL experiments. Y.C. and J.K. designed and carried out the TEM and MSR pore analysis experiments. O.A.A. contributed to the study design.

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Correspondence to David J. Mooney.

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Li, A.W., Sobral, M.C., Badrinath, S. et al. A facile approach to enhance antigen response for personalized cancer vaccination. Nature Mater 17, 528–534 (2018). https://doi.org/10.1038/s41563-018-0028-2

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