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

Authors :: Ruella M
Xu J
Barrett DM
Fraietta JA
Reich TJ
Ambrose DE
Klichinsky M
Shestova O
Patel PR
Kulikovskaya I
Nazimuddin F
Bhoj VG
Orlando EJ
Fry TJ
Bitter H
Maude SL
Levine BL
Nobles CL
Bushman FD
Young RM
Scholler J
Gill SI
June CH
Grupp SA
Lacey SF
Melenhorst JJ
Source :: Nature medicine [Nat Med] 2018 Oct; Vol. 24 (10), pp. 1499-1503. Date of Electronic Publication: 2018 Oct 01.
Publication Year :: 2018
Abstract: We report a patient relapsing 9 months after CD19-targeted CAR T cell (CTL019) infusion with CD19 <superscript>-</superscript> 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.

Subjects :: Adult
Antigens, CD19 therapeutic use
B-Lymphocytes immunology
Cell- and Tissue-Based Therapy
Humans
Leukemia immunology
Leukemia pathology
Male
Receptors, Antigen, T-Cell immunology
Receptors, Antigen, T-Cell therapeutic use
Receptors, Chimeric Antigen
T-Lymphocytes immunology
Young Adult
Antigens, CD19 immunology
Drug Resistance, Neoplasm immunology
Epitopes immunology
Leukemia drug therapy

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