Wu et al. generated supramolecular α-helical peptide nanofiber vaccines including an EGFRvIII receptor B cell peptide epitope, a melanoma-associated TRP CD8+ T cell peptide epitope, and a tetanus toxoid CD4+ T cell epitope. Relative to CFA-peptide emulsions, the nanofiber multi-targeting vaccine induced comparable T cell responses and higher titers of specific antibodies, which mediated tumor lysis and phagocytosis by cells in vitro. In s.c. EGFRvIII+ melanoma mouse models, prophylactic and therapeutic vaccination induced antitumor effects exceeding those induced by controls; these effects were improved by anti-PD-L1 + anti-CD47 blocking antibodies.
Contributed by Paula Hochman
ABSTRACT: Subunit vaccines inducing antibodies against tumor-specific antigens have yet to be clinically successful. Here, we use a supramolecular α-helical peptide nanofiber approach to design epitope-specific vaccines raising simultaneous B cell, CD8+ T cell, and CD4+ T cell responses against combinations of selected epitopes and show that the concurrent induction of these responses generates strong antitumor effects in mice, with significant improvements over antibody or CD8+ T cell-based vaccines alone, in both prophylactic and therapeutic subcutaneous melanoma models. Nanofiber vaccine-induced antibodies mediated in vitro tumoricidal antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). The addition of immune checkpoint and phagocytosis checkpoint blockade antibodies further improved the therapeutic effect of the nanofiber vaccines against murine melanoma. These findings highlight the potential clinical benefit of vaccine-induced antibody responses for tumor treatments, provided that they are accompanied by simultaneous CD8+ and CD4+ responses, and they illustrate a multiepitope cancer vaccine design approach using supramolecular nanomaterials.
Author Info: (1) Department of Biomedical Engineering, Duke University, Durham, NC, USA. (2) Department of Biomedical Engineering, Duke University, Durham, NC, USA. (3) Department of Biomedical
Author Info: (1) Department of Biomedical Engineering, Duke University, Durham, NC, USA. (2) Department of Biomedical Engineering, Duke University, Durham, NC, USA. (3) Department of Biomedical Engineering, Duke University, Durham, NC, USA. (4) Department of Biomedical Engineering, Duke University, Durham, NC, USA. (5) Department of Biomedical Engineering, Duke University, Durham, NC, USA. (6) Department of Neurosurgery, Duke University, Durham, NC, USA. (7) Department of Neurosurgery, Duke University, Durham, NC, USA. (8) Department of Neurosurgery, Duke University, Durham, NC, USA. (9) Department of Neurosurgery, Duke University, Durham, NC, USA. (10) Department of Biomedical Engineering, Duke University, Durham, NC, USA.
