Chemotherapy-induced nanovaccines implement immunogenicity equivalence for improving cancer chemoimmunotherapy

Rui Li; Yuhao Hao; Kyle Roche; Guiyuan Chen; Wen Pan; Andrew Z Wang; Yuanzeng Min

doi:10.1016/j.biomaterials.2023.122290

Chemotherapy-induced nanovaccines implement immunogenicity equivalence for improving cancer chemoimmunotherapy

Biomaterials. 2023 Oct:301:122290. doi: 10.1016/j.biomaterials.2023.122290. Epub 2023 Aug 21.

Authors

Rui Li¹, Yuhao Hao¹, Kyle Roche², Guiyuan Chen¹, Wen Pan¹, Andrew Z Wang³, Yuanzeng Min⁴

Affiliations

¹ Department of Chemistry, University of Science and Technology of China, Hefei, 230026, China.
² School of Medicine and Health Sciences, The George Washington University, Washington, DC 20052, USA.
³ Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
⁴ Department of Chemistry, University of Science and Technology of China, Hefei, 230026, China; Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, Anhui Provincial Hospital, University of Science and Technology of China, Hefei, 230026, China; CAS Key Lab of Soft Matter Chemistry, University of Science and Technology of China, Hefei, 230026, China. Electronic address: minyz@ustc.edu.cn.

PMID: 37643488
DOI: 10.1016/j.biomaterials.2023.122290

Abstract

Several chemoimmunotherapies have been approved by the FDA for the treatment of various cancers. Chemotherapy has the potential to improve the efficacy of immunotherapy by inducing immunogenic cell death (ICD) of tumor cells, promoting the release of tumor associated antigens (TAAs), tumor specific antigens (TSAs) and damage associated molecular patterns (DAMPs), and disrupting immunosuppressive microenvironments by tumor debulking. Unfortunately, systemic administration of chemotherapeutics carries side effects of blunting anti-cancer immune response through systemic immunosuppression, which deserves to be explored as an inner contradiction in chemoimmunotherapy. Here, we proposed the hypothesis of "immunogenicity equivalence" in chemoimmunotherapy that chemotherapeutics-induced immunogenic antigens and DAMPs in vitro that can subsequently be incorporated into nanovaccines, which will possess comparable immunostimulatory potential when compared to tumors treated with systemic chemotherapy in vivo. The proteomic analysis confirmed that our nanovaccines contained TAAs, TSAs and DAMPs. Improvement in treatment outcomes in tumor-bearing mice receiving anti-PD-1 and chemotherapy-induced nanovaccines was then observed. Furthermore, we demonstrated the feasibility of replacing long-term chemotherapy with nanovaccines in chemoimmunotherapy. Our nanovaccine strategy would be a general choice for formulating cancer vaccines in personalized medicine.

Keywords: Anti-PD-1; Chemoimmunotherapy; Damage associated molecular patterns; Nanovaccines; Neoantigens.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents*
Immunosuppression Therapy
Immunotherapy
Mice
Neoplasms* / drug therapy
Proteomics
Tumor Microenvironment

Substances

Antineoplastic Agents