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

Abstract

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, a novel strategy is reported 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-GD FD FD pY (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 increases antigen accumulation in the lymph nodes and cross-presentation by antigen-presenting cells (APCs). In addition, the inhibition of cyclooxygenase 2 (COX-2) expression by the nanofibers promotes the repolarization of M2-macrophages into M1 and reduces the number of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) required for TME remodeling. As a result, the combination of nanovaccines and RT significantly enhances the therapeutic effect on 4T1 tumors compared with RT alone, suggesting a promising treatment strategy for tumor radioimmunotherapy.

• Authors: Hongjing Luo, Hongmei Cao, Haixue Jia, Yuna Shang, Jinjian Liu, Han Gui, Cuihong Yang, Chunhua Ren, Zhongyan Wang, Jianfeng Liu
• Journal: Advanced healthcare materials (Adv Healthc Mater) Vol. 12 Issue 27 Pg. e2301083 (10 2023) ISSN: 2192-2659 [Electronic] Germany
• PMID: 37300544 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023 Wiley-VCH GmbH.

Chemical References

• Vaccines
• Peptides

Topics

• Humans
• Nanofibers
• Radioimmunotherapy
• Immunogenic Cell Death
• Immunotherapy (methods)
• Neoplasms (radiotherapy)
• Vaccines
• Peptides
• Inflammation
• Tumor Microenvironment
• Cell Line, Tumor