A platform for locoregional T-cell immunotherapy to control HNSCC recurrence following tumor resection
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Shay Sharon1, Jason R. Baird2, Shelly Bambina2, Gwen Kramer2, Tiffany C. Blair2,3, Shawn M. Jensen2, Rom S. Leidner2, R. Bryan Bell2, Nardy Casap1, Marka R. Crittenden2,4 and Michael J. Gough2
1 Department of Oral and Maxillofacial Surgery, Hadassah and Hebrew University Medical Center, Jerusalem 9112001, Israel
2 Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, Portland, OR 97213, USA
3 Department of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, OR 97239, USA
4 The Oregon Clinic, Portland, OR 97213, USA
|Michael J. Gough,||email:||[email protected]|
Keywords: head and neck cancer; T-cell; immunotherapy; biomaterial; intratumoral
Received: April 19, 2021 Accepted: May 26, 2021 Published: June 22, 2021
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.
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