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T-Cell Receptor Stimulation Enhances the Expansion and Function of CD19 Chimeric Antigen Receptor-Expressing T Cells.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2019 Dec 15; Vol. 25 (24), pp. 7340-7350. Date of Electronic Publication: 2019 Sep 26. - Publication Year :
- 2019
-
Abstract
- Purpose: Current protocols for CD19 chimeric antigen receptor-expressing T cells (CD19.CAR-T cells) require recipients to tolerate preinfusion cytoreductive chemotherapy, and the presence of sufficient target antigen on normal or malignant B cells.<br />Patients and Methods: We investigated whether additional stimulation of CD19.CAR-T cells through their native receptors can substitute for cytoreductive chemotherapy, inducing expansion and functional persistence of CD19.CAR-T even in patients in remission of B-cell acute lymphocytic leukemia. We infused a low dose of CD19.CAR-modified virus-specific T cells (CD19.CAR-VST) without prior cytoreductive chemotherapy into 8 patients after allogeneic stem cell transplant.<br />Results: Absent virus reactivation, we saw no CD19.CAR-VST expansion. In contrast, in patients with viral reactivation, up to 30,000-fold expansion of CD19.CAR-VSTs was observed, with depletion of CD19 <superscript>+</superscript> B cells. Five patients remain in remission at 42-60+ months.<br />Conclusions: Dual T-cell receptor and CAR stimulation can thus potentiate effector cell expansion and CAR-target cell killing, even when infusing low numbers of effector cells without cytoreduction.<br /> (©2019 American Association for Cancer Research.)
- Subjects :
- Adenoviridae physiology
Adolescent
Antigens, CD19 metabolism
Child
Child, Preschool
Genetic Vectors
Herpesvirus 4, Human physiology
Humans
Lymphoma, B-Cell immunology
Lymphoma, B-Cell virology
Precursor Cell Lymphoblastic Leukemia-Lymphoma immunology
Precursor Cell Lymphoblastic Leukemia-Lymphoma virology
Retroviridae physiology
T-Lymphocytes immunology
T-Lymphocytes virology
Young Adult
Antigens, CD19 immunology
Immunotherapy, Adoptive methods
Lymphoma, B-Cell therapy
Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
Receptors, Antigen, T-Cell immunology
T-Lymphocytes transplantation
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 25
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 31558475
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-18-3199