Targeting CD276: a promising strategy for CAR-NK cell immunotherapy in human oral tongue squamous cell carcinoma

Area of Science:

• Oncology
• Immunotherapy
• Biomarker Discovery

Background:

• Human oral tongue squamous cell carcinoma (OTSCC) is a significant subtype of head and neck squamous cell carcinoma (HNSCC).
• Advanced-stage OTSCC presents a poor prognosis with limited efficacy of current treatments like surgery, radiotherapy, and chemoradiotherapy.
• There is a critical need for novel therapeutic strategies to improve outcomes for OTSCC patients.

Purpose of the Study:

• To identify a novel therapeutic target for advanced OTSCC.
• To develop and evaluate chimeric antigen receptor-natural killer (CAR-NK) cell therapy targeting CD276 for OTSCC treatment.
• To assess the pre-clinical efficacy of CD276-targeted CAR-NK cells against OTSCC.

Main Methods:

• Bioinformatics analysis to identify significant biomarkers in OTSCC.
• Development of CAR-NK cells derived from umbilical cord blood cells (UCBCs) targeting the CD276 protein.
• In vitro and ex vivo studies involving OTSCC cell lines, primary cells, and organoids.

Main Results:

• CD276 was identified as a significant biomarker in OTSCC, with high expression correlating to reduced survival in late-stage patients.
• CD276-targeted CAR-NK cells demonstrated significant efficacy in lysing OTSCC cell lines and primary cells.
• The developed CAR-NK cells were effective in eliminating OTSCC organoids in pre-clinical models.

Conclusions:

• CD276 plays a crucial role in the pathogenesis of OTSCC.
• CD276-targeted CAR-NK cell therapy represents a promising and potentially groundbreaking treatment strategy for advanced-stage OTSCC.
• This novel immunotherapy offers new hope for translational medicine in stomatology for treating this challenging cancer.