A Modular Polymer Platform that Delivers Recombinant Cytokines and Cisplatin Allows for De-Escalation of Radiation Therapy in an Animal Model of Head and Neck Squamous Cell Carcinoma

Abstract

To evaluate the safety and efficacy of a novel modular polymer platform for head and neck squamous cell carcinoma (HNSCC). 50% of HNSCC patients fail primary management, and salvage of patients with recurrent disease is of paramount importance. We had previously shown the antitumor efficiency of this novel polymer in delivering chemokines (CCl21) and cisplatin in an animal model of SCCHN. Here we evaluate the safety and efficacy of this polymer in combination with radiation therapy (RT) in an effort to see if this combination allows for a de-escalation of RT. SCCVII/SF tumors were established in in C3H/HeJ mice. Tumors were then treated with either (1) no polymer, (2) plain polymer, (3) CCl21-polymer, (4) cisplatin polymer, and (5) combination CCl21 and cisplatin secreting polymer. The mice were then treated with three different doses of RT. Tumor size was measured every day until the mice were euthanized. Four weeks later, necropsy was performed to evaluate for vascular or nerve damage and to assess tumor size and weight. Cisplatin-polymer, CCL21-polymer, and the combination CCl21-cisplatin polymer effectively reduced SCCVII/SF tumors in the C3H/HeJ mice by over 16-fold (P<.01) as compared to control and plain polymer groups. Additionally, treatment with Cisplatin-polymer, CCL21-polymer and the combination CCl21-cisplatin polymer allowed for a 4-fold reduction in the dose of RT required. Histopathology revealed no adverse tissue effects when the cisplatin polymer was inserted in direct contact with the carotid artery, jugular vein or vagus nerve. Our promising results indicate that this polymer may represent a new therapeutic modality for patients with HNSCC that is safe and efficacious. Our data provides a strong rationale for further evaluation of this polymer in de-intensification of radiation therapy. 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.