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The 2022 Tandem Meetings | Mechanisms of antigen escape following CD19-directed CAR-T therapy

Pablo Domizi, PhD, Stanford University, Stanford, CA, describes the various mechanisms for antigen escape following CD19-directed CAR-T therapy. To begin with, mutations in the coding region of the CD19 gene can lead to no functional protein being produced. It has also been suggested that promoter hypermethylation can lead to silencing of the CD19 gene. Transdifferentiation is another mechanism that can mediate antigen escape following CAR-T therapy. In addition, recent experiments have shown that patients with lower levels of Ikaros prior to CAR-T administration may be predisposed to alternative splicing of CD19 ultimately resulting in CAR-T escape. Measuring Ikaros levels could therefore indicate whether a patient is likely to respond to CD19-directed CAR-T therapy. This interview took place at the Transplantation & Cellular Therapy (TCT) Meetings of ASTCT™ and CIBMTR® 2022 in Salt Lake City, Utah.