EISA in Tandem with ICD to form in Situ Nanofiber Vaccine for Enhanced Tumor Radioimmunotherapy.

Radiotherapy (RT) can produce a vaccine effect and remodel a tumor microenvironment (TME) by inducing immunogenic cell death (ICD) and inflammation in tumors. However, RT alone is insufficient to elicit a systemic antitumor immune response owing to limited antigen presentation, immunosuppressive microenvironment, and chronic inflammation within the tumor. Here, we report a novel strategy for the generation of in situ peptide-based nanovaccines via enzyme-induced self-assembly (EISA) in tandem with ICD. As ICD progresses, the peptide Fbp-pY, dephosphorylated by alkaline phosphatase (ALP), forms a fibrous nanostructure around the tumor cells, resulting in the capture and encapsulation of the autologous antigens produced by radiation. Utilizing the adjuvant and controlled-release advantages of self-assembling peptides, this nanofiber vaccine effectively increased antigen accumulation in the lymph nodes and cross-presentation by antigen-presenting cells. In addition, the inhibition of COX-2 expression by the nanofibers promoted the repolarization of M2-macrophages into M1 and reduced the number of Tregs and MDSCs required for TME remodeling. As a result, the combination of nanovaccines and RT significantly enhanced the therapeutic effect on 4T1 tumors compared with RT alone, suggesting a promising treatment strategy for tumor radioimmunotherapy. This article is protected by copyright. All rights reserved.