Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma.

Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma. Research Abstract Details 

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Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma. Abstract Text:

Julie R Park,David L Digiusto,Marilyn Slovak,Christine Wright,Araceli Naranjo,Jamie Wagner,Hunsar B Meechoovet,Cherrilyn Bautista,Wen-Chung Chang,Julie R Ostberg,Michael C Jensen,

Metastatic neuroblastoma is a poor-prognosis malignancy arising during childhood that overexpresses the L1-cell adhesion molecule (CD171). We have previously described a tumor L1-cell adhesion molecule-specific, single chain antibody-derived, chimeric antigen receptor designated CE7R for re-directing the antigen-specific effector functioning of cytolytic T lymphocytes. Here, we report on the feasibility of isolating, and the safety of infusing, autologous CD8(+) cytolytic T lymphocyte clones co-expressing CE7R and the selection-suicide expression enzyme HyTK in children with recurrent/refractory neuroblastoma. The cytolytic T lymphocyte products were derived from peripheral blood mononuclear cells that were subjected to polyclonal activation, plasmid vector electrotransfer, limiting dilution hygromycin selection, and expansion to numbers sufficient for adoptive transfer. In total, 12 infusions (nine at 10(8) cells/m(2), three at 10(9) cells/m(2)) were administered to six patients. No overt toxicities to tissues known to express L1-cell adhesion molecule (e.g., central nervous system, adrenal medulla, and sympathetic ganglia) were observed. The persistence of cytolytic T lymphocyte clones in the circulation, measured by vector-specific quantitative polymerase chain reaction, was short (1-7 days) in patients with bulky disease, but significantly longer (42 days) in a patient with a limited disease burden. This first-in-humans pilot study sets the stage for clinical trials employing adoptive transfer in the context of minimal residual disease.

Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma. Publishing Authors By Initials

JR Park,DL Digiusto,M Slovak,C Wright,A Naranjo,J Wagner,HB Meechoovet,C Bautista,WC Chang,JR Ostberg,MC Jensen,

For similar natural sciences: time: time factors research abstracts see: natural sciences: time: time factors research

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Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular therapy : the journal of the American So

VOLUME: 15

Page Numbers: 825-33

Journal Abbreviation: Mol. Ther.

ISSN: 1525-0016

DAY: 13

MONTH: 02

YEAR: 2007

Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma. Information

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LANGUAGE: eng

NlmUniqueID: 100890581

Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma. Keywords Mesh Terms:

KEYWORDS: Time Factors

MESH TERMS: immunology

Chemical & Substance for Abstract: Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma. Information

Substance Name: Recombinant Fusion Proteins

Registry Number: 0

Grant and Affiliation Information for Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma.

AFFILIATION: Department of Pediatric Hematology-Oncology, Children's Hospital and Medical Center, Seattle, Washington, USA.

Country: United States

AGENCY: United States NCI

GRANT: R21 CA105824

ACRONYM: CA

MEDLINETA: Mol Ther

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