Building on their previous porous silicon microrod vaccine, Li et al. enhanced the vaccine’s immune-stimulating and antigen-incorporating effects by adsorbing polyethyleneimine to the microrods. This enhanced the accumulation of activated dendritic cells at the vaccine site and draining lymph nodes, and increased the number and activation state of antigen-specific CD8+ T cells in the peripheral blood and the tumor. A single dose of the easily assembled vaccine resulted in significant tumor control in multiple viral and neoantigen vaccine tumor models and was synergistic with anti-CTLA-4.
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.
Author Info: (1) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. Wyss Institute for Biologically Inspired Engineering, Harvard University, Bo
Author Info: (1) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. (2) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. (3) Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA. (4) School of Chemical Engineering, Sungkyunkwan University, Suwon, Republic of Korea. (5) Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. (6) Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. (7) Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. (8) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. (9) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. (10) Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. (11) School of Chemical Engineering, Sungkyunkwan University, Suwon, Republic of Korea. Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science & Technology (SAIHST), Sungkyunkwan University, Suwon, Republic of Korea. Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon, Republic of Korea. (12) Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA. (13) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. mooneyd@seas.harvard.edu. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. mooneyd@seas.harvard.edu.
