Hydrogelation of peptides and carnosic acid as regulators of adaptive immunity against postoperative recurrence of cutaneous melanoma

The in-situ activation of adaptive immunity at the surgical site has demonstrated remarkable efficacy in inhibiting various forms of tumour recurrence and even holds the promise of a potential cure. However, extensive research and bioinformatic analysis conducted in this study have unveiled the formidable challenge posed by melanoma-intrinsic β-catenin signaling, which hinders the infiltration of cytotoxic T-lymphocytes (CTLs) and their subsequent anti-tumour action. To overcome this obstacle, a β-catenin antagonist called carnosic acid (CA) was co-assembled with a RADA-rich peptide to create a nanonet-derived hydrogel known as Supra-gelδCA. This injectable hydrogel is designed to be retained at the surgical site while simultaneously promoting hemostasis. Importantly, Supra-gelδCA directly releases CA to the site of residual tumour lesions, thereby enhancing infiltration of CTLs and subsequently activating adaptive immunity. Consequently, it effectively suppresses postoperative recurrence of skin cutaneous melanoma (SKCM) in vivo. Collectively, the presented Supra-gelδCA not only provides an efficacious immunotherapy strategy for regulating adaptive immunity by overcoming the obstacle posed by melanoma-intrinsic β-catenin signaling-induced absence of CTLs but also offers a clinically translatable hydrogel that revolutionizes post-surgical management of SKCM. [Display omitted]