Article
Convergence of Acquired Mutations and Alternative Splicing of CD19 Enables Resistance to CART-19 Immunotherapy.
Cancer discovery - 1 Dec 2015
Sotillo Elena, Barrett David M, Black Kathryn L, Bagashev Asen, Oldridge Derek, Wu Glendon, Sussman Robyn, Lanauze Claudia, Ruella Marco, Gazzara Matthew R, Martinez Nicole M, Harrington Colleen T, Chung Elaine Y, Perazzelli Jessica, Hofmann Ted J, Maude Shannon L, Raman Pichai, Barrera Alejandro, Gill Saar, Lacey Simon F, Melenhorst Jan J, Allman David, Jacoby Elad, Fry Terry, Mackall Crystal, Barash Yoseph, Lynch Kristen W, Maris John M, Grupp Stephan A, Thomas-Tikhonenko Andrei
Abstract excerpt
UNLABELLED: The CD19 antigen, expressed on most B-cell acute lymphoblastic leukemias (B-ALL), can be targeted with chimeric antigen receptor-armed T cells (CART-19), but relapses with epitope loss occur in 10% to 20% of pediatric responders. We detected hemizygous deletions spanning the CD19 locus and de novo frameshift and missense mutations in exon 2 of CD19 in some relapse samples. However, we also discovered...
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