Expression features of targets for anti-glioma CAR-T cell immunotherapy.

OBJECTIVE

To investigate the expression features of common anti-glioma CAR-T targets (B7H3, CSPG4, EGFRv III, HER2 and IL-13Ra2) in gliomas with different grades and molecular subtypes, and explore the association of target expression with glioma malignant or immune phenotypes including immune evasion, stemness, antigen presentation, and tumor angiogenesis.

METHODS

Opal™ Multiplex immunofluorescence staining was performed on glioma tissues to detect the expression of targets, and biomarkers related to the phenotypes.

RESULTS

High variety of CAR-T target expression among glioma subtypes was observed. GBMs exhibited the highest expression level of all the examined targets among glioma subtypes. In all glioma cases, CSPG4 was the most prevalent target covering over 84% glioma cases, followed by B7H3 at over 64%. B7H3 exhibited the highest coverage (94%) in GBMs while CSPG4 was the most popular target in both oligodendrogliomas and astrocytomas, covering 94% and 80% cases, respectively. Bi or tri-target combination strategies markedly expanded the tumor coverage across glioma cases while increased tumor-cell coverage within tumor. PD-L1 expression was significantly enriched in all the target-positive cells (except the EGFRvIII cells); CD133 expression was higher in the CSPG4 or IL-13Ra2 cells, and CD31 elevated in the B7H3 cells, as compared with their negative cell populations.

CONCLUSION

Anti-glioma CAR-T targets have heterogenous expression and distinct tumor coverage among glioma subtypes, and closely correlate with glioma malignant or immune phenotypes.