Intratumoral Administration of a Novel Cytotoxic Formulation with Strong Tissue Dispersive Properties Regresses Tumor Growth and Elicits Systemic Adaptive Immunity in In Vivo Models.

摘要: The recent development of immune-based therapies has improved the outcome for cancer patients; however, adjuvant remain an important line treatment several types. To maximize efficacy, checkpoint inhibitors are often combined with cytotoxic agents. While this approach leads to increased tumor regression, higher off target toxicity results in certain patients. This report describes a novel formulation comprising unique amphiphilic molecule, 8-((2-hydroxybenzoyl)amino)octanoate (SHAO), that non-covalently interacts payloads increase drug dispersion and diffusion when dosed intratumorally (IT) into solid tumors. SHAO is co-formulated cisplatin vinblastine (referred as INT230-6). IT dosing achieved greater growth inhibition survival vivo models compared same drugs without enhancer given intravenously or IT. INT230-6 immune infiltrating cells injected tumors 10% 20% animals having complete responses developing systemic immunity cancer. was also shown be synergistic programmed cell death protein 1 (PD-1) antibodies at improving increasing responses. induced significant necrosis potentially releasing antigens induce anti-cancer attack. research demonstrates novel, local minimizes while stimulating adaptive immunity.