Resumé
PURPOSE: T cells engineered to express a chimeric antigen receptor (CAR) against CD19 have recently been FDA-approved for the treatment of relapsed or refractory large B cell lymphoma. Despite the success and curative potential of CD19 CAR T cells, several reports describing disease relapse due to antigen loss are now emerging.
EXPERIMENTAL DESIGN: We developed a novel CAR construct directed against CD79b, a critical receptor for successful B cell development that remains highly expressed in several subtypes of B cell lymphoma, including mantle cell lymphoma (MCL). We tested CAR T cells directed against CD79b alone or in combination with CD19 targeting in a single construct, against cell line- and patient-derived xenograft models.
RESULTS: We demonstrate CAR79b antigen-specific recognition and cytotoxicity against a panel of cell lines and patient-derived xenograft models of MCL. Importantly, we show that downregulation of CD19 does not influence surface expression of CD79b and that anti-CD79b CAR T cells alone or arranged in a dual-targeting format with a CD19 single-chain variable fragment (scFv) are able to recognize and eliminate CD19-positive, CD19-negative, and mixed CD19+/CD19- B cell lymphoma.
CONCLUSIONS: Our findings demonstrate that CAR T cells targeting CD79b alone or in combination have promise for treating and preventing CD19 antigen escape in B cell lymphomas.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Clinical Cancer Research |
| ISSN | 1078-0432 |
| DOI | |
| Status | E-pub ahead of print - 22. aug. 2019 |
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Chimeric antigen receptor T cells targeting CD79b show efficacy in lymphoma with or without co-targeting CD19. / Ormhøj, Maria; Scarfò, Irene; Cabral, Maria L; Bailey, Stefanie R; Lorrey, Selena J; Bouffard, Amanda A; Castano, Ana P; Larson, Rebecca C; Riley, Lauren S; Schmidts, Andrea; Choi, Bryan D; Andersen, Rikke S; Cédile, Oriane; Nyvold, Charlotte Guldborg; Haaber, Jacob; Gjerstorff, Morten F; Ditzel, Henrik J; Weinstock, David M; Barington, Torben; Frigault, Matthew J; Maus, Marcela V.
I: Clinical Cancer Research, 22.08.2019.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
TY - JOUR
T1 - Chimeric antigen receptor T cells targeting CD79b show efficacy in lymphoma with or without co-targeting CD19
AU - Ormhøj, Maria
AU - Scarfò, Irene
AU - Cabral, Maria L
AU - Bailey, Stefanie R
AU - Lorrey, Selena J
AU - Bouffard, Amanda A
AU - Castano, Ana P
AU - Larson, Rebecca C
AU - Riley, Lauren S
AU - Schmidts, Andrea
AU - Choi, Bryan D
AU - Andersen, Rikke S
AU - Cédile, Oriane
AU - Nyvold, Charlotte Guldborg
AU - Haaber, Jacob
AU - Gjerstorff, Morten F
AU - Ditzel, Henrik J
AU - Weinstock, David M
AU - Barington, Torben
AU - Frigault, Matthew J
AU - Maus, Marcela V
N1 - Copyright ©2019, American Association for Cancer Research.
PY - 2019/8/22
Y1 - 2019/8/22
N2 - PURPOSE: T cells engineered to express a chimeric antigen receptor (CAR) against CD19 have recently been FDA-approved for the treatment of relapsed or refractory large B cell lymphoma. Despite the success and curative potential of CD19 CAR T cells, several reports describing disease relapse due to antigen loss are now emerging.EXPERIMENTAL DESIGN: We developed a novel CAR construct directed against CD79b, a critical receptor for successful B cell development that remains highly expressed in several subtypes of B cell lymphoma, including mantle cell lymphoma (MCL). We tested CAR T cells directed against CD79b alone or in combination with CD19 targeting in a single construct, against cell line- and patient-derived xenograft models.RESULTS: We demonstrate CAR79b antigen-specific recognition and cytotoxicity against a panel of cell lines and patient-derived xenograft models of MCL. Importantly, we show that downregulation of CD19 does not influence surface expression of CD79b and that anti-CD79b CAR T cells alone or arranged in a dual-targeting format with a CD19 single-chain variable fragment (scFv) are able to recognize and eliminate CD19-positive, CD19-negative, and mixed CD19+/CD19- B cell lymphoma.CONCLUSIONS: Our findings demonstrate that CAR T cells targeting CD79b alone or in combination have promise for treating and preventing CD19 antigen escape in B cell lymphomas.
AB - PURPOSE: T cells engineered to express a chimeric antigen receptor (CAR) against CD19 have recently been FDA-approved for the treatment of relapsed or refractory large B cell lymphoma. Despite the success and curative potential of CD19 CAR T cells, several reports describing disease relapse due to antigen loss are now emerging.EXPERIMENTAL DESIGN: We developed a novel CAR construct directed against CD79b, a critical receptor for successful B cell development that remains highly expressed in several subtypes of B cell lymphoma, including mantle cell lymphoma (MCL). We tested CAR T cells directed against CD79b alone or in combination with CD19 targeting in a single construct, against cell line- and patient-derived xenograft models.RESULTS: We demonstrate CAR79b antigen-specific recognition and cytotoxicity against a panel of cell lines and patient-derived xenograft models of MCL. Importantly, we show that downregulation of CD19 does not influence surface expression of CD79b and that anti-CD79b CAR T cells alone or arranged in a dual-targeting format with a CD19 single-chain variable fragment (scFv) are able to recognize and eliminate CD19-positive, CD19-negative, and mixed CD19+/CD19- B cell lymphoma.CONCLUSIONS: Our findings demonstrate that CAR T cells targeting CD79b alone or in combination have promise for treating and preventing CD19 antigen escape in B cell lymphomas.
U2 - 10.1158/1078-0432.CCR-19-1337
DO - 10.1158/1078-0432.CCR-19-1337
M3 - Journal article
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
ER -