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A platform for locoregional T-cell immunotherapy to control HNSCC recurrence following tumor resection
- Source :
- Oncotarget
- Publication Year :
- 2021
- Publisher :
- Impact Journals LLC, 2021.
-
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.
- Subjects :
- Oncology
medicine.medical_specialty
business.industry
medicine.medical_treatment
T cell
Head and neck cancer
biomaterial
Immunotherapy
medicine.disease
intratumoral
Lymphatic system
Immune system
medicine.anatomical_structure
Antigen
T-cell
Internal medicine
medicine
Carcinoma
Adjuvant therapy
head and neck cancer
immunotherapy
business
Research Paper
Subjects
Details
- Language :
- English
- ISSN :
- 19492553
- Volume :
- 12
- Issue :
- 13
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....aee4f99de7488e784f12872b2b0c5e66