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Otolaryngol Head Neck Surg. 2014 Sep;151(3):447-53. doi: 10.1177/0194599814533775. Epub 2014 May 13.

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

Author information

1
Department of Head and Neck Surgery, University of California, Los Angeles, Los Angeles, California, USA UCLA Head and Neck Cancer Program, University of California, Los Angeles, Los Angeles, California, USA Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
2
Department of Bioengineering, University of California, Los Angeles, Los Angeles, California, USA.
3
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Los Angeles, Los Angeles, California, USA Veterans' Affairs Greater Los Angeles Healthcare System, Los Angeles, California, USA.
4
Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, California, USA.
5
Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California, USA Department of Biostatistics, University of California, Los Angeles, Los Angeles, California, USA.
6
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Los Angeles, Los Angeles, California, USA Veterans' Affairs Greater Los Angeles Healthcare System, Los Angeles, California, USA Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California, USA.
7
Department of Bioengineering, University of California, Los Angeles, Los Angeles, California, USA Division of Advanced Prosthodontics, Biomaterials, and Hospital Dentistry, University of California, Los Angeles, Los Angeles, California, USA Department of Materials Science and Engineering, University of California, Los Angeles, Los Angeles, California, USA Department of Orthopedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
8
Department of Head and Neck Surgery, University of California, Los Angeles, Los Angeles, California, USA UCLA Head and Neck Cancer Program, University of California, Los Angeles, Los Angeles, California, USA Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California, USA mstjohn@mednet.ucla.edu.

Abstract

OBJECTIVE:

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).

STUDY DESIGN:

In vivo study.

SETTING:

Academic research laboratory.

SUBJECTS AND METHODS:

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).

RESULTS:

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).

CONCLUSION:

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.

KEYWORDS:

head and neck cancer; novel therapeutics; polymer; squamous cell carcinoma

PMID:
24825873
PMCID:
PMC4167678
DOI:
10.1177/0194599814533775
[Indexed for MEDLINE]
Free PMC Article
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