CD70 as a target for chimeric antigen receptor T cells in head and neck squamous cell carcinoma.

Oral Oncology
Yuk Pheel ParkEdward K L Chan

Abstract

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. 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. 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 can...Continue Reading

Citations

Feb 6, 2020·Molecular Carcinogenesis·Samantha M Y ChenJing H Wang
Jan 23, 2021·Expert Review of Clinical Immunology·Azadehsadat RazaviNima Rezaei
Jan 5, 2021·Journal of Oral Microbiology·Amani M HarrandahEdward K L Chan
Jun 12, 2021·Frontiers in Neuroscience·Luke MaggsSoldano Ferrone

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