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PMID: 16352804 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Differentiation of naive cord-blood T cells into CD19-specific cytolytic effectors for posttransplantation adoptive immunotherapy.

Blood ·Vol. 107 ·No. 7 ·2006-04-01 ·Pages 2643-52

Serrano LM, Pfeiffer T, Olivares S, Numbenjapon T, Bennitt J, Kim D, Smith D, McNamara G, Al-Kadhimi Z, Rosenthal J, Forman SJ, Jensen MC, Cooper LJ

Abstract

Disease relapse is a barrier to achieving therapeutic success after unrelated umbilical cord-blood transplantation (UCBT) for B-lineage acute lymphoblastic leukemia (B-ALL). While adoptive transfer of donor-derived tumor-specific T cells is a conceptually attractive approach to eliminating residual disease after allogeneic hematopoietic stem cell transplantation, adoptive immunotherapy after UCBT is constrained by the difficulty of generating antigen-specific T cells from functionally naive umbilical cord-blood (UCB)-derived T cells. Therefore, to generate T cells that recognize B-ALL, we have developed a chimeric immunoreceptor to redirect the specificity of T cells for CD19, a B-lineage antigen, and expressed this transgene in UCB-derived T cells. An ex vivo process, which is compliant with current good manufacturing practice for T-cell trials, has been developed to genetically modify and numerically expand UCB-derived T cells into CD19-specific effector cells. These are capable of CD19-restricted cytokine production and cytolysis in vitro, as well as mediating regression of CD19+ tumor and being selectively eliminated in vivo. Moreover, time-lapse microscopy of the genetically modified T-cell clones revealed an ability to lyse CD19+ tumor cells specifically and repetitively. These data provide the rationale for infusing UCB-derived CD19-specific T cells after UCBT to reduce the incidence of CD19+ B-ALL relapse.

MeSH Terms
Animals Antigens, CD/blood Antigens, CD19/blood Burkitt Lymphoma/immunology,therapy Cell Death Cell Survival Cytotoxicity, Immunologic Fetal Blood/immunology,transplantation Ganciclovir/pharmacology Humans Immunotherapy Immunotherapy, Adoptive K562 Cells Luminescent Measurements Lymphocyte Depletion/methods Lymphocyte Transfusion Mice Microscopy, Video T-Lymphocytes/immunology
Chemicals
Antigens, CD Antigens, CD19 Ganciclovir
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Serrano Lisa Marie
University of Texas M. D. Anderson Cancer Center, Pediatrics Research Unit 853, 1515 Holcombe Blvd, Houston, TX 77030, USA.
Pfeiffer Timothy
Olivares Simon
Numbenjapon Tontanai
Bennitt Jennifer
Kim Daniel
Smith David
McNamara George
Al-Kadhimi Zaid
Rosenthal Joseph
Forman Stephen J
Jensen Michael C
Cooper Laurence J N
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
DOI
10.1182/blood-2005-09-3904
Published
2006-04-01
Epub
2005-00-13
Pages
2643-52
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC1895371
Subset
IM
Grants
NCI NIH HHS · CA003572 · United States
NCI NIH HHS · CA107399 · United States
NCI NIH HHS · CA30206 · United States
External Links
PubMed source DOI: 10.1182/blood-2005-09-3904 PMC Full Text View journal details
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