(625) Immune profiling of the effects of a local cisplatin-eluting polymer combined with radiation

Introduction: As limited tolerability of systemic therapies in head and neck squamous cell carcinoma (HNSCC) can limit treatment options for advanced-stage cancers, more work is required on developing alternate modalities with less morbidity. Surgically implanted devices, such as drug-eluting polymers and gold nanostars, provide an opportunity to augment the effects of radiation and allow deescalation of therapy.

Methods: Forty male HeJ mice were sorted into the following treatment groups: control polymer, polymer with gold nanostars (GNS), polymer with cisplatin (Pt), and polymer with GNS and Pt. These mice were implanted with SCC tumors; after the tumors grew to a volume of 1 cm³, they were debulked by 50% to mimic a situation where a tumor cannot be resected completely. Following this debulking procedure, the polymers were implanted. Each of these mice was treated with either no radiotherapy (RT) or RT at doses of 4 or 2 Gray (Gy) for 4 treatments. Tumor growth was measured daily for 40 days. At the end of the experiment, mice were sacrificed and tumors from mice treated with GNS/Pt, GNS/Pt with 4Gy of radiation, and control polymers were collected for immunofluorescence staining.

Results: The addition of cisplatin or increased dosages of radiation resulted in reduced tumor growth (p < 0.001). Interestingly, reduced doses of radiation in mice implanted with GNS/Pt polymer yielded similar outcomes compared to mice treated with cisplatin and full strength radiation (p = 0.8471). Cisplatin with partial or full-dose radiation outperformed GNS polymer with full dose radiation (p < 0.001). Immune profiling revealed differences in proportions of tumor invading lymphocytes in mice that underwent GNS/Pt versus plain polymer in a contact-dependent fashion.

Conclusions: This novel drug-eluting polymer provides a potential alternative treatment pathway for patients unable to tolerate cisplatin. Gold nanostars function as radiation sensitizers and are able to augment the effects of radiation such that reduced dosages are effective. This has impactful implications in affording patients lower doses of radiation.