Perspective for CAR T-Cell Therapy in Underrepresented Populations: A Hypothesis-Generating CD19 Genomic Analysis.
Among Arab individuals, the CD19 L174V valine/valine genotype was very common
Perspective for CAR T-Cell Therapy in Underrepresented Populations: A Hypothesis-Generating CD19 Genomic Analysis.
CD19-directed chimeric antigen receptor (chimeric antigen receptor) T-cell therapy has fundamentally transformed the treatment landscape for relapsed and refractory B-cell malignancies, yet antigen escape remains a persistent therapeutic challenge that limits long-term remission durability.
We analyzed publicly available whole-exome sequencing data from 1196 individuals of Arab origin to comprehensively characterize CD19 variants with potential relevance to chimeric antigen receptor T-cell immunotherapy.
65.3% carried two copies of the valine version of the CD19 gene
While antigen loss is typically considered a somatic event acquired during tumor evolution under therapeutic selective pressure, germline CD19 polymorphisms could theoretically influence chimeric antigen receptor-binding kinetics, alter epitope presentation, and modulate therapeutic outcomes in ways that remain largely not characterized.
The missense mutation (c.520C > G) responsible for this variant results in a leucine-to-valine (L174V) substitution at position 174 of the CD19 protein, relative to the reference genome.
The cohort genotypes (CC, CG, and GG) exhibited a significant deviation from Hardy-Weinberg equilibrium ( p < 0.00001).
Instead, it presents a unique opportunity to investigate the clinical relevance of germline variation in the context of precision oncology, particularly at therapy-relevant loci, pending functional validation.