A Fluorinated Supramolecular Self‐Assembled Peptide as Nanovaccine Adjuvant for Enhanced Cancer Vaccine Therapy

Abstract Adjuvants play an important role in enhancing vaccine‐induced immune protection. Adequate cellular uptake, robust lysosomal escape, and subsequent antigen cross‐presentation are critical steps for vaccine adjuvants to effectively elicit cellular immunity. Here, a fluorinated supramolecular strategy to generate a series of peptide adjuvants by using arginine (R) and fluorinated diphenylalanine peptide (DP) is adopted. It is found that the self‐assembly ability and antigen‐binding affinity of these adjuvants increase with the number of fluorine (F) and can be regulated by R. By comparison, 4RDP(F5) shows the strongest binding affinity with model antigen ovalbumin (OVA) and the best performance in dendritic cells maturation and antigen's lysosomal escape, which contributes to the subsequent antigen cross‐presentation. As a consequence, 4RDP(F5)‐OVA nanovaccine generates a strong cellular immunity in a prophylactic OVA‐expressing EG7‐OVA lymphoma model, leading to long‐term immune memory for resisting tumor challenge. What's more, 4RDP(F5)‐OVA nanovaccine in combination with anti‐programmed cell death ligand‐1 (anti‐PD‐L1) checkpoint blockade could effectively elicit anti‐tumor immune responses and inhibit tumor growth in a therapeutic EG7‐OVA lymphoma model. Overall, this study demonstrates the simplicity and effectiveness of fluorinated supramolecular strategies for constructing adjuvants and might provide an attractive vaccine adjuvant candidate for cancer immunotherapy.