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A Model for Perineural Invasion in Head and Neck Squamous Cell Carcinoma
Published on: January 5, 2017
CD70 as a target for chimeric antigen receptor T cells in head and neck squamous cell carcinoma
Yuk Pheel Park1, Linchun Jin2, Katie B Bennett1
1Department of Oral Biology, University of Florida, Gainesville, FL 32610, USA.
Objectives:
In accordance with the Precision Medicine Initiative, new treatment strategies for head and neck squamous cell carcinoma (HNSCC) are needed to yield better therapeutic outcomes. The purpose of this study was to establish and validate chimeric antigen receptor (CAR)-T cells targets in HNSCC.
Methods:
Putative CAR-T antigens were identified in The Cancer Genome Atlas database. To validate antigen suitability, quantitative RT-PCR, flow cytometry, and immunofluorescent staining were performed. A retroviral human CD70 CAR construct, using truncated CD27 conjugated with 4-1BB and CD3-zeta costimulatory molecules, was used to transduce activated human T cells to generate CD70 CAR-T cells. Cell-based cytotoxicity and cytokine ELISAs were used to measure efficacy of killing.
Results:
Nine potential CAR-T targets (CD276, EGFR, MICA, MICB, MAGE-A4, FAP, EPCAM, CD70, B4GALNT1) were identified based on their high expression in tumors compared to flanking control tissues. CD70 was selected for further proof-of-principle analysis based on its differential expression in several tumor subtypes, and showed substantial heterogeneity in individual tumors analyzed. Cell surface CD70 protein and CD70 mRNA were detected from low to high levels in established HNSCC cancer cell lines. CD70 was highly expressed in 4 of 21 tumor biopsies (19%), and 3 of 4 specimens showed strong CD70 expression on the tumor cell surface. CD70-specific CAR-T cells were generated and further demonstrated to recognize and kill CD70-positive HNSCC cells efficiently, but not CD70-negative cancer cells.
Conclusion:
CD70-specific CAR-T cells specifically recognized and efficiently eliminated CD70-positive HNSCC cells. This study provides the basis for further investigation into CD70 and other CAR-T targets.
Insights
Chimeric antigen receptor (CAR)-T cells targeting CD70 show promise for treating head and neck squamous cell carcinoma (HNSCC). These engineered T cells effectively recognized and eliminated CD70-positive HNSCC cells in vitro.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Biology
Background:
- Head and neck squamous cell carcinoma (HNSCC) requires novel treatment strategies for improved outcomes.
- Precision Medicine Initiative highlights the need for targeted therapies in HNSCC.
Purpose of the Study:
- To identify and validate potential targets for chimeric antigen receptor (CAR)-T cell therapy in HNSCC.
- To establish and test the efficacy of CD70-specific CAR-T cells against HNSCC.
Main Methods:
- Identified potential CAR-T targets using The Cancer Genome Atlas database.
- Validated antigen expression via quantitative RT-PCR, flow cytometry, and immunofluorescence.
- Generated CD70 CAR-T cells and assessed their cytotoxic activity and cytokine production in vitro.
Main Results:
- Nine potential CAR-T targets were identified, with CD70 selected for further study.
- CD70 expression was confirmed at mRNA and protein levels in HNSCC cell lines and patient biopsies.
- CD70-specific CAR-T cells demonstrated efficient killing of CD70-positive HNSCC cells but not CD70-negative cells.
Conclusions:
- CD70-specific CAR-T cells effectively target and eliminate CD70-positive HNSCC cells.
- This study supports CD70 as a viable target for HNSCC immunotherapy and warrants further investigation.
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