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


METHODS
In vivo study.


METHODS
Academic research laboratory.


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).


CONCLUSIONS
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.
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.
Yuan
Y
Lin
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.
Jie
J
Luo
Department of Bioengineering, University of California, Los Angeles, Los Angeles, California, USA.
Weichao Eric
WE
Zhu
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.
Minu
M
Srivastava
Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, California, USA.
Dorthe
D
Schaue
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.
David A
DA
Elashoff
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.
Steven M
SM
Dubinett
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.
Sherven
S
Sharma
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.
Benjamin
B
Wu
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.
Maie A
MA
St John
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D002945:Cisplatin / Q000008:administration & dosage*; D016207:Cytokines / Q000494:pharmacology*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004343:Drug Implants; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011108:Polymers / Q000494:pharmacology*; D011897:Random Allocation; D015996:Survival Rate; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
D016207:Cytokines; D004343:Drug Implants; D011108:Polymers; D002945:Cisplatin
head and neck cancer; novel therapeutics; polymer; squamous cell carcinoma