Use of a Novel Polymer in an Animal Model of Head and Neck Squamous Cell Carcinoma

Peter A Pellionisz; Yuan Lin; Jon Mallen-St Clair; Jie Luo; Arnold Suwarnasarn; Dorthe Schaue; David A Elashoff; Fernando Palma-Diaz; Steven M Dubinett; Sherven Sharma; Ben Wu; Maie A St John

doi:10.1177/0194599817730304

Use of a Novel Polymer in an Animal Model of Head and Neck Squamous Cell Carcinoma

Otolaryngol Head Neck Surg. 2018 Jan;158(1):110-117. doi: 10.1177/0194599817730304. Epub 2017 Sep 12.

Authors

Peter A Pellionisz^{1

2

3}, Yuan Lin^{4

5}, Jon Mallen-St Clair^{1

2}, Jie Luo^{4

5}, Arnold Suwarnasarn³, Dorthe Schaue⁶, David A Elashoff^{2

7}, Fernando Palma-Diaz⁸, Steven M Dubinett^{4

5

9}, Sherven Sharma^{4

5

9}, Ben Wu^{3

10

11

12}, Maie A St John^{1

2

13}

Affiliations

¹ 1 Department of Head and Neck Surgery, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
² 2 Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
³ 3 Department of Bioengineering, Henry Samueli School of Engineering and Applied Sciences, University of California, Los Angeles, California, USA.
⁴ 4 Lung Cancer Research Program, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
⁵ 5 Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
⁶ 6 Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
⁷ 7 Department of Biostatistics, University of California, Los Angeles, California, USA.
⁸ 8 Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
⁹ 9 Veterans' Affairs Greater Los Angeles Healthcare System, Los Angeles, California, USA.
¹⁰ 10 Division of Advanced Prosthodontics, Biomaterials, and Hospital Dentistry, University of California, Los Angeles, California, USA.
¹¹ 11 Department of Materials Science and Engineering, University of California, Los Angeles, California, USA.
¹² 12 Department of Orthopedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
¹³ 13 Head and Neck Cancer Program, David Geffen School of Medicine, University of California, Los Angeles, California, USA.

PMID: 28895464
DOI: 10.1177/0194599817730304

Abstract

Objective To evaluate the adverse effects and therapeutic efficacy of our biocompatible polymer platform delivering targeted local therapy of cytokine CCL21 and cisplatin in a partially resected xenograft animal model of head and neck squamous cell carcinoma. In addition, to evaluate the efficacy of cotreatment with radiotherapy and assess the biocompatibility of the cisplatin-eluting polymer in the murine neck. Study Design Experimental animal study. Setting Academic research laboratory. Subjects and Methods SCCVII/SF cell injection established head and neck squamous cell carcinoma tumors in C3H/HeJ mice. Subjects underwent surgery, and a chemokine-eluting polymer was implanted into the resected site. Subjects treated with cisplatin received radiation or no radiation, and tissue was harvested after 8 weeks to assess polymer biocompatibility. Results Our results with the polymer platform significantly ( P < .05) reduced SCCVII/SF tumor size in C3H/HeJ mice with cisplatin (49% ± 8.7%, Δ3.4 ± 0.6 cm³ [95% CI]), CCL21 (42% ± 4.8%, Δ3.5 ± 0.4 cm³), and cisplatin/CCL21 dual-agent polymer (82% ± 4.4%, Δ8.0 ± 0.4 cm³) as compared with controls. Cisplatin polymer with high-dose (16 Gy) and low-dose (4 Gy) radiation reduced tumor mass (respectively, 92% ± 7.2%, Δ6.1 ± 0.5 cm³; 85% ± 7.4%, Δ5.7 ± 0.5 cm³) as compared with the reduction from high-dose radiotherapy alone (70% ± 7.9%, Δ4.7 ± 0.5 cm³). No significant toxicity or inflammation was noted on histopathology after radiotherapy and cisplatin-eluting polymer treatment. Conclusion Cisplatin, CCL21, and cisplatin/CCL21 dual-agent polymer all exhibit significant antitumor effects and decrease tumor burden. Moreover, combination cisplatin polymer with radiotherapy may permit a decrease in intensity of radiation therapy in patients having received the cisplatin polymer. Histopathologic analysis suggests that the polymer is free from significant adverse effects in this model and warrants clinical trial.

Keywords: head and neck cancer; novel therapeutics; polymer; squamous cell carcinoma.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biocompatible Materials / pharmacology
Carcinoma, Squamous Cell / drug therapy*
Chemokine CCL21 / administration & dosage*
Cisplatin / administration & dosage*
Disease Models, Animal
Drug Delivery Systems*
Enzyme-Linked Immunosorbent Assay
Head and Neck Neoplasms / drug therapy*
Mice
Polyesters / pharmacology
Polymers / pharmacology*

Substances

Biocompatible Materials
Chemokine CCL21
Polyesters
Polymers
polycaprolactone
poly(lactide)
Cisplatin

Grants and funding

R01 CA220663/CA/NCI NIH HHS/United States