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Cited by 408

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Construction and Preclinical Evaluation of an Anti-CD19 Chimeric Antigen Receptor

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Kochenderfer, James N., Feldman, Steven A., Zhao, Yangbing, Xu, Hui, Black, Mary A., Morgan, Richard A., Wilson, Wyndham H., Rosenberg, Steven A.·2009·Journal of Immunotherapy
DOI 10.1097/cji.0b013e3181ac6138
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Abstract

T cells can be engineered to express the genes of chimeric antigen receptors (CARs) that recognize tumor-associated antigens. We constructed and compared 2 CARs that contained a single chain variable region moiety that recognized CD19. One CAR contained the signaling moiety of the 4-1BB molecule and the other did not. We selected the CAR that did not contain the 4-1BB moiety for further preclinical development. We demonstrated that gammaretroviruses encoding this receptor could transduce human T cells. Anti-CD19-CAR-transduced CD8+ and CD4+ T cells produced interferon-gamma and interleukin-2 specifically in response to CD19+ target cells. The transduced T cells specifically killed primary chronic lymphocytic leukemia (CLL) cells. We transduced T cells from CLL patients that had been previously treated with chemotherapy. We induced these T cells to proliferate sufficiently to provide enough cells for clinical adoptive T cell transfer with a protocol consisting of an initial stimulation with an anti-CD3 monoclonal antibody (OKT3) before transduction followed by a second OKT3 stimulation 7 days after transduction. This protocol was successfully adapted for use in CLL patients with high peripheral blood leukemia cell counts by depleting CD19+ cells before the initial OKT3 stimulation. In preparation for a clinical trial that will enroll patients with advanced B cell malignancies, we generated a producer cell clone that produces retroviruses encoding the anti-CD19 CAR, and we produced sufficient retroviral supernatant for the proposed clinical trial under good manufacturing practice conditions.

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  • Two subsets of memory T lymphocytes with distinct homing potentials and effector functions

    Sallusto, F., Lenig, D., Förster, R., Lipp, M., & Lanzavecchia, A. (1999) · Nature · doi:10.1038/44385 · Cited by 5,846 · cited 1×

    “The phenotype of these T cells is generally that of an effector memory T cell.(62) These effector memory T cells can mediate objective regressions of melanoma in approximately 50% of patients when they are infused as part of a treatment protocol that includes lymphocyte-depleting chemotherapy before cell infusion and…”
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Metadata

Authors
Kochenderfer, J. N., Feldman, S. A., Zhao, Y., Xu, H., Black, M. A., Morgan, R. A., Wilson, W. H., & Rosenberg, S. A.
Venue
Journal of Immunotherapy
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2009-09
Volume
32
Issue
7
Pages
689-702
ISSN
1524-9557 (ISSN-L)
DOI
10.1097/cji.0b013e3181ac6138
OpenAlex
W1974431455
Cited by
408
References
1
FWCI
3.43
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Construction and Preclinical Evaluation of an Anti-CD19 Chimeric Antigen Receptor. https://app.cochat.ai/papers/10.1097/cji.0b013e3181ac6138
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Kochenderfer, J. N., Feldman, S. A., Zhao, Y., Xu, H., Black, M. A., Morgan, R. A., Wilson, W. H., & Rosenberg, S. A. (2009). Construction and Preclinical Evaluation of an Anti-CD19 Chimeric Antigen Receptor. Journal of Immunotherapy. https://doi.org/10.1097/cji.0b013e3181ac6138

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