Abstract P4-07-63: Local delivery of immunotherapeutics as an in situ vaccine in triple negative breast cancer

Abstract

Abstract Introduction. Breast cancer (BC) is among the most common types of cancer among women, with an estimated 287,850 new cases and 43,250 deaths in 2022 [1]. Triple negative breast cancer (TNBC), characterized by lack of ER/PR/HER2 receptors, constitutes 10-15% of diagnosed BC and correlates with the worst prognosis and most aggressive form of the disease [2]. Additionally, compared to the other BC subtypes, TNBC have higher rates of recurrence and highest therapy resistance [2]. Because TNBC lacks a clearly defined target, in situ vaccination may pose a viable therapy option, to locally stimulate an immune response and thereby reduce the tumor burden and prevent recurrence and metastasis. To this end, we developed an injectable delivery medium to effectively localize immune agonists at the site of the tumor. Materials and methods. Hydrogel delivery medium: Low-viscosity, high-deacetylated chitosan was crosslinked with 1-ethyl-3-(-3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide at room temperature overnight. The mixture was dialyzed and freeze-dried. A hydrogel was formed by dissolving the chitosan in deionized water at concentrations from 25-50 mg/mL. In vivo tumor treatment: 1e5 E0771 breast cancer cells were implanted subcutaneously in the right flank of C57BL/6 mice. When tumors were 50-100mm3, mice were treated intratumorally with 50ug Poly(I:C) + 50ug CpG in 30 mg/mL chitosan gel, with 50ug Poly(I:C) + 50ug CpG in saline, or with gel alone. In the second experiment, to enhance the anti-tumor effect of the immunotherapeutic, 2ug of the cytokine interleukin-12 in the chitosan gel will be delivered intratumorally. All experiments involving laboratory animals were approved by the Institutional Animal Care and Use Committee at North Carolina State University. Results and Discussion. The gel was effectively localized within the tumor environment upon injection. The localized Poly(I:C) + CpG in the gel demonstrated an enhanced anti-tumor effect, compared to gel alone. Ongoing work will determine the efficacy of administering the cytokine IL-12. Acknowledgements. This work is supported by an NSF Graduate Research Fellowship. References. [1] Siegel R, et al. CA A Cancer J Clin (2022) 72(1):7-33. [2] Retecki K, et al. Cancers (2021) 13(23):6012 Citation Format: Siena Mantooth, David Zaharoff. Local delivery of immunotherapeutics as an in situ vaccine in triple negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-63.