A Novel Modular Polymer Platform for the Treatment of Head and Neck Squamous Cell Cancer

Abstract

Objectives: Evaluate the therapeutic efficacy of a novel modular polymer platform in the treatment of head and neck squamous cell carcinoma (HNSCC). 50% of HNSCC patients fail primary management, and salvage of the recurrent disease patient is of paramount importance. Methods: Study Design: In vivo study. Setting: Academic research laboratory. C3H/HeJ mice were randomized to receive implantation of 1) no polymer; 2) plain polymer; 3) plain polymer containing gene-modified dendritic cells over-expressing CCL21 (DC-AdCCL21); and 4) plain polymer with concurrent daily CCL21 injections. 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 remarkable reduction in tumor growth. The dendritic cell CCL21 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, and plain polymer + intratumoral CCL21 injection groups. We also demonstrate that we can effectively grow dendritic cells in the polymer that can actively secrete CCL21. Treatment with the dendritic cell CCL21 secreting polymer led to a marked reduction in tumor burden with extensive mononuclear cell infiltration of the tumors. Conclusions: Our promising results indicate that this polymer may represent a new therapeutic modality for patients with HNSCC. Our data provide a strong rationale for further evaluation of this DC-AdCCL21 polymer in regulation of tumor immunity and genetic immunotherapy for HNSCC. Once this polymer platform is further optimized, we will plan for the ultimate validation in the context of a prospective trial in patients with unresectable advanced or recurrent HNSCC.