A platform for locoregional T-cell immunotherapy to control HNSCC recurrence following tumor resection.
oregon; portland; chiles
Surgical resection of head and neck squamous-cell carcinoma (HNSCC) is associated with high rates of local and distant recurrence, partially mitigated by adjuvant therapy. A pre-existing immune response in the patient's tumor is associated with better outcomes following treatment with conventional therapies, but improved options are needed for patients with poor anti-tumor immunity. We hypothesized that local delivery of tumor antigen-specific T-cells into the resection cavity following surgery would direct T-cells to residual antigens in the margins and draining lymphatics and present a platform for T-cell-targeted immunotherapy. We loaded T-cells into a biomaterial that conformed to the resection cavity and demonstrated that it could release T-cells that retained their functional activity in-vitro, and in a HNSCC model in-vivo. Locally delivered T-cells loaded in a biomaterial were equivalent in control of established tumors to intravenous adoptive T-cell transfer, and resulted in the systemic circulation of tumor antigen-specific T-cells as well as local accumulation in the tumor. We demonstrate that adjuvant therapy with anti-PD1 following surgical resection was ineffective unless combined with local delivery of T-cells. These data demonstrate that local delivery of tumor-specific T-cells is an efficient option to convert tumors that are unresponsive to checkpoint inhibitors to permit tumor cures.
Earle A. Chiles Research Institute
Allergy & Immunology
Sharon, Shay; Baird, Jason R; Bambina, Shelly; Kramer, Gwen; Blair, Tiffany C; Jensen, Shawn M; Leidner, Rom S; Bell, R Bryan; Casap, Nardy; Crittenden, Marka R; and Gough, Michael J, "A platform for locoregional T-cell immunotherapy to control HNSCC recurrence following tumor resection." (2021). Articles, Abstracts, and Reports. 5049.