Abstract 4581: A novel modular polymer platform for the treatment of oral and head and neck carcinoma

Abstract

Abstract Objective: Head and neck Squamous cell carcinoma (HNSCC) is difficult to resect completely by surgery due to complicated context and therefore exhibits high recurrence rate in the patient. To reduce tumor recurrence after surgery, we developed a biodegradable polymer to deliver CCL21 cytokine and cisplatin, and evaluate its efficacy in a partially resected xenograft animal model of HNSCC. Study Design: in vivo study. Setting: Academic research laboratory. Subjects and Methods: After xenograft HNSCC tumors were established by subcutaneous injection, C3H/HeJ mice underwent surgery to debulk their tumors to a size of 0.5x0.5x0.5 cm3 and received different polymer implantation. For cytokine studies, mice were grouped into: (1) no polymer; (2) plain polymer; (3) plain polymer with intratumoral injection of recombinant CCL21 twice a week; (4) polymer containing parental dendritic cells; (5) polymer containing dendritic cells secreting CCL21 (DC-CCL21). For cisplatin studies, mice were randomized to receive implantation of (1) no polymer; (2) plain polymer; (3) plain polymer with local cisplatin injection; (4) cisplatin polymer. The two groups of mice implanted with cisplatin polymer or no polymer were further randomized to receive (1) 4 Grays external beam radiation for 4 days; (2) no radiation. Tumor size was measured until the mice were euthanized. At necropsy, the tumors were excised and weighed. Results: Our results using this novel polymer platform demonstrate a significant reduction in tumor growth. The DC-CCL21 polymer reduced SCCVII/SF tumors in the C3H/HeJ mice by over 41% compared to the control groups (p<0.01). The cisplatin secreting polymer effectively reduced SCCVII/SF tumors in the C3H/HeJ mice by over 16-fold (P < 0.01) as compared to control, plain polymer group. We also observed a statistically significant lower tumor weight among mice treated with cisplatin polymer and concomitant CCL21 compared to the control group. Conclusion: Herein we demonstrate the efficacy of a novel polymer platform in delivering cisplatin and cytokines to a partially resected SCC in a murine model. We also demonstrate that we can effectively grow dendritic cells in the polymer that can actively secrete CCL21. Our results indicate that this polymer may represent a new therapeutic modality for patients with HNSCC. Once this polymer platform is optimized we will plan for validation in the context of a prospective trial in patients with unresectable advanced or recurrent HNSCC. Citation Format: Yuan Lin, Sherven Sharma, Steven M. Dubinett, Ben Wu, Maie St. John. A novel modular polymer platform for the treatment of oral and head and neck carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4581. doi:10.1158/1538-7445.AM2014-4581