Oncotarget

Research Papers:

A platform for locoregional T-cell immunotherapy to control HNSCC recurrence following tumor resection

Shay Sharon, Jason R. Baird, Shelly Bambina, Gwen Kramer, Tiffany C. Blair, Shawn M. Jensen, Rom S. Leidner, R. Bryan Bell, Nardy Casap, Marka R. Crittenden and Michael J. Gough _

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Oncotarget. 2021; 12:1201-1213. https://doi.org/10.18632/oncotarget.27982

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Abstract

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

Correspondence to:

Michael J. Gough,email: michael.gough@providence.org

Keywords: head and neck cancer; T-cell; immunotherapy; biomaterial; intratumoral

Received: April 19, 2021     Accepted: May 26, 2021     Published: June 22, 2021

Copyright: © 2021 Sharon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

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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