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PMID: 20668228 Published · ppublish English Clinical Trial Journal Article Research Support, N.I.H., Intramural

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

Blood ·Vol. 116 ·No. 20 ·2010-11-18 ·Pages 4099-102

Kochenderfer JN, Wilson WH, Janik JE, Dudley ME, Stetler-Stevenson M, Feldman SA, Maric I, Raffeld M, Nathan DA, Lanier BJ, Morgan RA, Rosenberg SA

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.

MeSH Terms
Antigens, CD19/immunology B-Lymphocytes/cytology Cell Lineage/immunology Genetic Engineering Humans Lymphocyte Depletion Lymphoma/immunology,therapy Male Receptors, Antigen/immunology Remission Induction T-Lymphocytes/immunology,transplantation Transduction, Genetic Transplantation, Autologous
Chemicals
Antigens, CD19 Receptors, Antigen
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Kochenderfer James N
Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA. kochendj@mail.nih.gov
Wilson Wyndham H
Janik John E
Dudley Mark E
Stetler-Stevenson Maryalice
Feldman Steven A
Maric Irina
Raffeld Mark
Nathan Debbie-Ann N
Lanier Brock J
Morgan Richard A
Rosenberg Steven A
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
1528-0020
DOI
10.1182/blood-2010-04-281931
Email
kochendj@mail.nih.gov
Published
2010-11-18
Epub
2010-00-28
Pages
4099-102
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC2993617
Subset
IM
Grants
Intramural NIH HHS · United States
Databases
ClinicalTrials.gov
NCT00924326
External Links
PubMed source DOI: 10.1182/blood-2010-04-281931 PMC Full Text View journal details
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