Chemotherapy-Induced Neoantigen Nanovaccines Enhance Checkpoint Blockade Cancer Immunotherapy

Authors

Guiyuan Chen, Department of Chemistry, University of Science and Technology of China, Hefei 230026, China.
Xiangxia Li, Department of Chemistry, University of Science and Technology of China, Hefei 230026, China.
Rui Li, Department of Chemistry, University of Science and Technology of China, Hefei 230026, China.
Kecheng Wu, Department of Chemistry, University of Science and Technology of China, Hefei 230026, China.
Zhouhang Lei, Department of Chemistry, University of Science and Technology of China, Hefei 230026, China.
Ruike Dai, Department of Chemistry, University of Science and Technology of China, Hefei 230026, China.
Kyle Roche, School of Medicine and Health Sciences, The George Washington University, Washington D.C. 20052, United States.
Andrew Z. Wang, Department of Radiation Oncology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, United States.
Yuanzeng Min, Department of Chemistry, University of Science and Technology of China, Hefei 230026, China.

Document Type

Journal Article

Publication Date

10-10-2023

Journal

ACS nano

Volume

17

Issue

19

DOI

10.1021/acsnano.3c03274

Keywords

chemotherapy; immune checkpoint inhibitors; immunogenicity; immunotherapy; nanovaccine

Abstract

Chemotherapeutics have the potential to increase the efficacy of cancer immunotherapies by stimulating the production of damage-associated molecular patterns (DAMPs) and eliciting mutations that result in the production of neoantigens, thereby increasing the immunogenicity of cancerous lesions. However, the dose-limiting toxicity and limited immunogenicity of chemotherapeutics are not sufficient to induce a robust antitumor response. We hypothesized that cancer cells treated with ultrahigh doses of various chemotherapeutics artificially increased the abundance, variety, and specificity of DAMPs and neoantigens, thereby improving chemoimmunotherapy. The chemotherapy-induced (IVCI) nanovaccines manufactured from cell lysates comprised multiple neoantigens and DAMPs, thereby exhibiting comprehensive antigenicity and adjuvanticity. Our IVCI nanovaccines exhibited enhanced immune responses in CT26 tumor-bearing mice, with a significant increase in CD4/CD8 T cells in tumors in combination with immune checkpoint inhibitors. The concept of IVCI nanovaccines provides an idea for manufacturing and artificial enhancement of immunogenicity vaccines to improve chemoimmunotherapy.

APA Citation

Chen, Guiyuan; Li, Xiangxia; Li, Rui; Wu, Kecheng; Lei, Zhouhang; Dai, Ruike; Roche, Kyle; Wang, Andrew Z.; and Min, Yuanzeng, "Chemotherapy-Induced Neoantigen Nanovaccines Enhance Checkpoint Blockade Cancer Immunotherapy" (2023). GW Authored Works. Paper 3623.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/3623

Department

School of Medicine and Health Sciences Resident Works