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Open AccessArticle

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

Intensity Therapeutics, Inc., Westport, CT 06880, USA
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Int. J. Mol. Sci. 2020, 21(12), 4493; https://doi.org/10.3390/ijms21124493
Received: 26 May 2020 / Revised: 10 June 2020 / Accepted: 21 June 2020 / Published: 24 June 2020
(This article belongs to the Special Issue The Immune Landscape in Solid Tumors)
The recent development of immune-based therapies has improved the outcome for cancer patients; however, adjuvant therapies remain an important line of treatment for several cancer types. To maximize efficacy, checkpoint inhibitors are often combined with cytotoxic agents. While this approach often leads to increased tumor regression, higher off target toxicity often results in certain patients. This report describes a novel formulation comprising a unique amphiphilic molecule, 8-((2-hydroxybenzoyl)amino)octanoate (SHAO), that non-covalently interacts with payloads to increase drug dispersion and diffusion when dosed intratumorally (IT) into solid tumors. SHAO is co-formulated with cisplatin and vinblastine (referred to as INT230-6). IT dosing of the novel formulation achieved greater tumor growth inhibition and improved survival in in vivo tumor models compared to the same drugs without enhancer given intravenously or IT. INT230-6 treatment increased immune infiltrating cells in injected tumors with 10% to 20% of the animals having complete responses and developing systemic immunity to the cancer. INT230-6 was also shown to be synergistic with programmed cell death protein 1 (PD-1) antibodies at improving survival and increasing complete responses. INT230-6 induced significant tumor necrosis potentially releasing antigens to induce the systemic immune-based anti-cancer attack. This research demonstrates a novel, local treatment approach for cancer that minimizes systemic toxicity while stimulating adaptive immunity. View Full-Text
Keywords: intratumoral; INT230-6; dispersion; diffusion; cytotoxic; cisplatin; vinblastine; cell-penetration; enhancer; immune activation; PD-1; antibody; CTLA-4; checkpoint intratumoral; INT230-6; dispersion; diffusion; cytotoxic; cisplatin; vinblastine; cell-penetration; enhancer; immune activation; PD-1; antibody; CTLA-4; checkpoint
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MDPI and ACS Style

Bender, L.H.; Abbate, F.; Walters, I.B. Intratumoral Administration of a Novel Cytotoxic Formulation with Strong Tissue Dispersive Properties Regresses Tumor Growth and Elicits Systemic Adaptive Immunity in In Vivo Models. Int. J. Mol. Sci. 2020, 21, 4493.

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