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Cited by 1,337CAR-T cell therapy researchT-cell and B-cell ImmunologyImmunotherapy and Immune Responses

Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19

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Kochenderfer, James N., Wilson, Wyndham H., Janik, John E., Dudley, Mark E., Stetler-Stevenson, Maryalice, Feldman, Steven A., Maric, Irina, Raffeld, Mark +4 more·2010·Blood
DOI 10.1182/blood-2010-04-281931PMC PMC2993617
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Abstract

Adoptive transfer of genetically modified T cells is an attractive approach for generating antitumor immune responses. We treated a patient with advanced follicular lymphoma by administering a preparative chemotherapy regimen followed by autologous T cells genetically engineered to express a chimeric antigen receptor (CAR) that recognized the B-cell antigen CD19. The patient's lymphoma underwent a dramatic regression, and B-cell precursors were selectively eliminated from the patient's bone marrow after infusion of anti-CD19-CAR-transduced T cells. Blood B cells were absent for at least 39 weeks after anti-CD19-CAR-transduced T-cell infusion despite prompt recovery of other blood cell counts. Consistent with eradication of B-lineage cells, serum immunoglobulins decreased to very low levels after treatment. The prolonged and selective elimination of B-lineage cells could not be attributed to the chemotherapy that the patient received and indicated antigen-specific eradication of B-lineage cells. Adoptive transfer of anti-CD19-CAR-expressing T cells is a promising new approach for treating B-cell malignancies. This study is registered at www.clinicaltrials.gov as #NCT00924326.

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  • Most clinical protocols and all commercially approved therapies have relied on viral vectors to deliver CAR transgenes into T cells.

    “Further, most clinical protocols, and all the commercially approved therapies, have relied on viral vectors to deliver CAR transgenes into T cells (9-14,24-26).”

    From Scalable Manufacturing of CAR T Cells for Cancer Immunotherapy (2021) · cites this paper as [12]

    The Methods (page not provided) describe a clinical trial that used a retroviral vector to deliver an anti-CD19 CAR into T cells. This supports the paper as an example of a viral-vector clinical protocol, but it does not establish that most protocols or all commercially approved therapies used viral vectors. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • All approved CAR T-cell products are second-generation CARs that incorporate CD28 or CD137 (4-1BB) co-stimulatory signals.

    “All approved CAR T-cell products are second-generation CARs that incorporate CD28 or CD137 (4-1BB) co-stimulatory signals, which are essential for eliciting effector and memory cell expansion and persistence and a clinically relevant immune response (9-15).”

    From Scalable Manufacturing of CAR T Cells for Cancer Immunotherapy (2021) · cites this paper as [12]

    The Methods (page not provided) describe this study’s anti-CD19 CAR as containing CD28 and CD3ζ signaling domains, and the Results and discussion report activity in one treated patient. The paper does not establish that all approved CAR T-cell products use CD28 or CD137, or that these signals are essential for effector and memory-cell expansion and persistence. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Most CAR T cell trials to date have used autologous peripheral blood and apheresis as the main cell sources for manufacturing.

    “First, most CAR T cell trials to date have used autologous peripheral blood and apheresis as the main cell sources for manufacturing (9-18,21,22).”

    From Scalable Manufacturing of CAR T Cells for Cancer Immunotherapy (2021) · cites this paper as [12]

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Research works printed but not linked: 25

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Sorted by citations

Authors
Kochenderfer, J. N., Wilson, W. H., Janik, J. E., Dudley, M. E., Stetler-Stevenson, M., Feldman, S. A., Maric, I., Raffeld, M., Nathan, D.-A. N., Lanier, B. J., Morgan, R. A., & Rosenberg, S. A.
Affiliations
  • Surgery Branch,
  • Metabolism Branch, and
  • Laboratory of Pathology, National Cancer Institute, Bethesda, MD; and
  • Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD
  • National Cancer Institute (US)
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
2010-11-18
Volume
116
Issue
20
Pages
4099-4102
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood-2010-04-281931
PMC
PMC2993617
OpenAlex
W1966542058
Cited by
1,337
References
0
Citations by year
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FWCI
31.18
Type
journal article
Language
en
Open access
Locations
  • Blood (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institutes of Health
Topics
  • Health Sciences › Medicine › Oncology › CAR-T cell therapy research
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
follicular lymphoma, chimeric antigen receptor T cells, CD19, adoptive T cell therapy, B cell precursors, bone marrow, serum immunoglobulins, B-cell malignancies
MeSH terms
B-Lymphocytes, Genetic Engineering, Humans, Lymphocyte Depletion, Lymphoma, Male, Receptors, Antigen, Remission Induction, T-Lymphocytes, Transduction, Genetic, Transplantation, Autologous, Antigens, CD19, Cell Lineage

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