Multiepitope supramolecular peptide nanofibers eliciting coordinated humoral and cellular antitumor immune responses

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.

Quantitative Ratiometric Biosensors Based on Fluorescent Ferrocene-Modified Histidine Dipeptide Nanoassemblies

“…Quantification analysis of peptides or proteins by EM needs the label of proteins and peptides with Au or other quantum dot (QDs). Quantification by EM is available in the concentration range from 0.001 μg/mL to 0.4 mg/mL, but the counts have a nonlinear relationship with the concentration of target biomolecules, and the analysis range for high concentrations is limited to their high cytotoxicity. , Our study here provides a feasible strategy for quantitative analysis of the peptides of interest through modular design with ratiometric f -HH dipeptide chromophores, which can work at concentrations ranging from 0.1 to 10 mg/mL, and these concentrations are relevant for the disease or animal model of interest as peptide materials typically have concentrations ranging from micromoles to millimoles, i.e., peptide carriers of siRNA (10 mg/mL), supramolecular peptide vaccine (0–2 mM), , and injectable antitumor peptide hydrogels (4 mg/mL) . Although the methods we provide are not as good as those described above at the trace analysis level, the ratiometric f -HH dipeptide is a biocompatible, accurate, and convenient platform for quantitative analysis of the peptides of interest.…”

Peptide Hydrogels and Nanostructures Controlling Biological Machinery

“…Previously, Q11 peptide nanofibers were able to act as an effective adjuvant and elicit a robust CD8+ T cell response, protecting mice from a challenge with influenza . More recently, a multiepitope antitumor vaccine utilizing supramolecular α-helical peptide nanofibers generated strong antitumor effects in mice by engaging both innate and adaptive immune responses . These findings highlight the potential of biomaterials for increasing the safety and efficacy of immunomodulatory therapies and developing effective vaccines against various diseases.…”

Self-assembling peptides as immunomodulatory biomaterials

“…A large number of SAPs are being explored for their potential in biomedical applications. In particular, MultiDomain Peptides (MDPs), Self-Assembling Amphiphilic Peptide Drug Conjugate (SAAPDC), RADARADARADARADA (RADA16), KLDLKLDLKLDL (KLD-12), SSGGPLGVRGKLVFFCAWSATWSNYWRH (LMY1), QAR-ILEADAEILRAYARILEAHAEILRAD (Coil-29), AEAEAKAKAEAEAKAK (EAK16-II), and QQKFQFQFEQQ (Q11) with their respective current immunotherapy strategies will be reviewed (Table 1) (Tripathi et al, 2015;Ding et al, 2016;Moore and Hartgerink, 2017;Mora-Solano et al, 2017;Ji et al, 2018;Wang et al, 2019;Lv et al, 2022;Wu et al, 2022).…”

“…Coil29 contains peptides with PEPvIII, B cell peptide epitope against EGFRvIII receptors, TRP2, a melanoma-associated CD8 T cell peptide antigen, and toxoid (Td) CD4 T cell epitope (Wu et al, 2022). After three subcutaneous immunizations with Coil29, the vaccine formulation containing three antigens PEPvIII, TRP2, and Toxoid (P/Tr/Td-fiber) and the Coil-29 with two antigens PEPvIII and Td (P/Td-fiber) both generated long-lasting PEPvIII-specific IgG responses compared to Complete Freund's Adjuvant with the three antigens.…”