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A cytokine-delivering polymer is effective in reducing tumor burden in a head and neck squamous cell carcinoma murine model

Authors :
Minu K Srivastava
Yuan Lin
Benjamin M. Wu
David Elashoff
Jie Luo
Steven M. Dubinett
Maie A. St. John
Sherven Sharma
Dörthe Schaue
Weichao Eric Zhu
Source :
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 151(3)
Publication Year :
2014

Abstract

This study aimed to evaluate the therapeutic efficacy of a novel polymer platform delivering cisplatin and cytokines in the treatment of head and neck squamous cell carcinoma (HNSCC).In vivo study.Academic research laboratory.Mice were randomized to receive implantation of (1) no polymer, (2) plain polymer, (3) plain polymer with local cisplatin injection, or (4) cisplatin polymer. The 2 groups of mice implanted with cisplatin polymer or no polymer were further randomized to receive (1) 4 Grays external beam radiation for 4 days or (2) no radiation. 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, or (5) polymer containing dendritic cells secreting CCL21 (DC-CCL21).The cisplatin-secreting polymer effectively reduced tumors in the mice by more than 16-fold (P.01). We also observed a statistically significant lower tumor weight among mice treated with cisplatin polymer and concomitant radiation compared to control groups. The DC-CCL21 polymer reduced SCCVII/SF tumors in the C3H/HeJ mice by more than 41% (P.01).Herein, we demonstrate the efficacy of a novel polymer platform in delivering cisplatin and cytokines. We also demonstrate that we can effectively grow dendritic cells in the polymer that can actively secrete CCL21 for a minimum of 5 days. This polymer may represent a new therapeutic modality for patients with HNSCC. Once this polymer platform is optimized, we will plan to pursue prospective trials in patients with HNSCC.

Details

ISSN :
10976817
Volume :
151
Issue :
3
Database :
OpenAIRE
Journal :
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery
Accession number :
edsair.doi.dedup.....ce2d8aba0e7c403be0f17439d2b3d71a