Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell. (October 2018)

• Record Type: Journal Article
• Authors: Ruella, Marco; Xu, Jun; Barrett, David; Fraietta, Joseph; Reich, Tyler; Ambrose, David; Klichinsky, Michael; Shestova, Olga; Patel, Prachi; Kulikovskaya, Irina; Nazimuddin, Farzana; Bhoj, Vijay; Orlando, Elena; Fry, Terry; Bitter, Hans; Maude, Shannon; Levine, Bruce; Nobles, Christopher; Bushman, Frederic; Young, Regina; Scholler, John; Gill, Saar; June, Carl; Grupp, Stephan; Lacey, Simon; Melenhorst, J.
• Is Part Of: Nature medicine. Volume 24:Number 10(2018)
• Page Start: 1499
• Page End: 1503
• Publication Date: 2018-10
• Subjects: Pathology, Molecular -- Periodicals; Molecular biology -- Periodicals; 610.724
• DOI: 10.1038/s41591-018-0201-9
• Languages: English
• ISSNs: 1078-8956

Abstract

Abstract We report a patient relapsing 9 months after CD19-targeted CAR T cell (CTL019) infusion with CD19– leukemia that aberrantly expressed the anti-CD19 CAR. The CAR gene was unintentionally introduced into a single leukemic B cell during T cell manufacturing, and its product bound in cis to the CD19 epitope on the surface of leukemic cells, masking it from recognition by and conferring resistance to CTL019. A CAR gene unintentionally introduced in a contaminating leukemia cell during the manufacturing of CAR T cells caused a patient to relapse after therapy.