Abstract 1224: Intratumoral chitosan/IL-12 neoadjuvant to tumor resection is safe and generates tumor specific immunity.

Abstract

Interleukin-12 (IL-12) is a potent antitumor cytokine that exhibits significant clinical toxicities after systemic administration. Local delivery strategies capable of maintaining high concentrations of IL-12 in the tumor microenvironment while minimizing systemic exposure are under investigation. We have previously shown that intratumoral injections of IL-12 co-formulated with a solution of chitosan (chitosan/IL-12) can eliminate established primary tumors. Chitosan is an abundant, natural polysaccharide derived primarily from the exoskeletons of crustaceans. Chitosan has been shown to maintain high local concentrations of protein antigens and cytokines through viscous, electrostatic and bioadhesive interactions.

Because of IL-12’s well documented ability to generate tumor-specific cell-mediated immunity, we are exploring the anti-metastatic potential of intratumoral chitosan/IL-12 immunotherapy in a highly metastatic model of breast cancer (4T1). Previously, we have shown that intratumoral chitosan/IL-12 neoadjuvant prior to tumor resection confers long-term survival benefits and reduces metastasis. Recent studies reveal that chitosan/IL-12 is safe and generates tumor-specific systemic immunity to confer long-term survival benefits. Specifically, splenocytes from long term survivors demonstrated anti-tumor immunity in a cytotoxic T-lymphocyte (CTL) killing assay. After 1 week of in vitro stimulation, splenocytes were found to lyse approximately 40% of target tumor cells at an effector: target ratio of 50:1. In addition, toxicological studies reveal that chitosan/IL-12 does not adversely affect leukocyte levels or hematocrit. Based on data obtained thus far, intratumoral chitosan/IL-12 shows promising potential as a neoadjuvant immunotherapy to reduce metastatic disease while minimizing the toxicities that hindered the progress of IL-12 based cancer immunotherapy.

Citation Format: Jimmy Loc Nhu Vo, Lirong Yang, David Zaharoff. Intratumoral chitosan/IL-12 neoadjuvant to tumor resection is safe and generates tumor specific immunity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1224. doi:10.1158/1538-7445.AM2013-1224