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

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.