Thermosensitive hydrogel delivery of BCG lysates and tumor antigens: A novel strategy for melanoma immunoprevention and therapeutics

Yanwei Chen; Li Zhang; Huashan Shi; Zhixue Shen; Dan Huang; Shuo Tang; Yueyue He; Guilan Wang; Hailong Pan; Zhenling Wang

doi:10.1016/j.bbrc.2024.151215

Thermosensitive hydrogel delivery of BCG lysates and tumor antigens: A novel strategy for melanoma immunoprevention and therapeutics

Biochem Biophys Res Commun. 2024 Dec 18:745:151215. doi: 10.1016/j.bbrc.2024.151215. Online ahead of print.

Authors

Yanwei Chen¹, Li Zhang¹, Huashan Shi², Zhixue Shen¹, Dan Huang¹, Shuo Tang³, Yueyue He¹, Guilan Wang¹, Hailong Pan⁴, Zhenling Wang⁵

Affiliations

¹ Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
² Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
³ Chengdu Institute of Biological Products Company Limited, Chengdu, 610023, China.
⁴ China National Biotec Group Company Limited, Beijing, 100000, China.
⁵ Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address: wangzhenling@scu.edu.cn.

PMID: 39732120
DOI: 10.1016/j.bbrc.2024.151215

Abstract

Melanoma, recognized as one of the most aggressive forms of skin cancer, continues to show a steady rise in global incidence. While Bacillus Calmette-Guérin (BCG) has been identified as a potential intralesional therapy for melanoma, its therapeutic efficacy remains suboptimal. This study introduces a novel thermosensitive hydrogel formulated with BCG lysates and either OVA peptide or tumor cell lysates (PPP-BCG-OVA/TL). The hydrogel demonstrated the ability to elicit a robust systemic tumor antigen-specific T cell response and significantly enhanced the infiltration of CD45⁺ leukocytes, macrophages, CD8⁺ T cells, and natural killer (NK) cells into the tumor microenvironment. As a result, vaccination with PPP-BCG-OVA/TL hydrogel effectively inhibited tumor growth and extended survival in mouse models of subcutaneous melanoma in both preventive and therapeutic contexts. These findings highlight the potential to markedly improve the therapeutic efficacy of BCG lysates through the addition of tumor antigens and the use of a hydrogel-based delivery platform.

Keywords: BCG; Hydrogel; Melanoma; Tumor antigen; Tumor lysate; Tumor vaccine.