Chimeric antigen receptors for stem cell based immunotherapy

Michael S. Badowski, Tong Zhang, Tom C. Tsang, David T. Harris

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The retargeting of lymphocytes is an important new strategy in immunotherapy of cancer. One can currently isolate naturally refined, high affinity specificities from antibodies and T-cell receptors (TCRs) to use in engineered applications. We have developed two new molecules that have specificity for the overexpressed tumor antigen HER2/neu. The specificity derived from an anti-HER2 antibody variable fragment was used to create a single chain Fv (scFv). A HER2 reactive TCR was also used to develop a single chain TCR (scTCR). The HER2 binding elements were linked to an intracellular signaling module, active only in the T cell signaling pathway, providing a novel molecule to retarget lymphocytes. We demonstrate here that these molecules can be expressed in several cell lines as well as in hematopoietic stem cells (HSCs). In a transplant setting, these new receptors can be expressed in multiple cells types derived from repopulating HSCs. These new chimeric receptors will be valuable tools for further research of immune function of retargeted hematopoietic cells.

Original languageEnglish (US)
Pages (from-to)53-63
Number of pages11
JournalJournal of Experimental Therapeutics and Oncology
Volume8
Issue number1
StatePublished - 2009

Fingerprint

Antigen Receptors
Hematopoietic Stem Cells
T-Cell Antigen Receptor
Immunotherapy
Stem Cells
Lymphocytes
T-Cell Antigen Receptor Specificity
Single-Chain Antibodies
Immunoglobulin Fragments
Antibody Affinity
Neoplasm Antigens
Anti-Idiotypic Antibodies
T-Lymphocytes
Transplants
Cell Line
Research
Neoplasms

Keywords

  • Cancer
  • Chimeric antigen receptor
  • HER2
  • Immunotherapy
  • Stem cell

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Cancer Research

Cite this

Chimeric antigen receptors for stem cell based immunotherapy. / Badowski, Michael S.; Zhang, Tong; Tsang, Tom C.; Harris, David T.

In: Journal of Experimental Therapeutics and Oncology, Vol. 8, No. 1, 2009, p. 53-63.

Research output: Contribution to journalArticle

Badowski, Michael S. ; Zhang, Tong ; Tsang, Tom C. ; Harris, David T. / Chimeric antigen receptors for stem cell based immunotherapy. In: Journal of Experimental Therapeutics and Oncology. 2009 ; Vol. 8, No. 1. pp. 53-63.
@article{21427b0414b744a49f58ecd16aa8be6f,
title = "Chimeric antigen receptors for stem cell based immunotherapy",
abstract = "The retargeting of lymphocytes is an important new strategy in immunotherapy of cancer. One can currently isolate naturally refined, high affinity specificities from antibodies and T-cell receptors (TCRs) to use in engineered applications. We have developed two new molecules that have specificity for the overexpressed tumor antigen HER2/neu. The specificity derived from an anti-HER2 antibody variable fragment was used to create a single chain Fv (scFv). A HER2 reactive TCR was also used to develop a single chain TCR (scTCR). The HER2 binding elements were linked to an intracellular signaling module, active only in the T cell signaling pathway, providing a novel molecule to retarget lymphocytes. We demonstrate here that these molecules can be expressed in several cell lines as well as in hematopoietic stem cells (HSCs). In a transplant setting, these new receptors can be expressed in multiple cells types derived from repopulating HSCs. These new chimeric receptors will be valuable tools for further research of immune function of retargeted hematopoietic cells.",
keywords = "Cancer, Chimeric antigen receptor, HER2, Immunotherapy, Stem cell",
author = "Badowski, {Michael S.} and Tong Zhang and Tsang, {Tom C.} and Harris, {David T.}",
year = "2009",
language = "English (US)",
volume = "8",
pages = "53--63",
journal = "Journal of Experimental Therapeutics and Oncology",
issn = "1359-4117",
publisher = "Old City Publishing",
number = "1",

}

TY - JOUR

T1 - Chimeric antigen receptors for stem cell based immunotherapy

AU - Badowski, Michael S.

AU - Zhang, Tong

AU - Tsang, Tom C.

AU - Harris, David T.

PY - 2009

Y1 - 2009

N2 - The retargeting of lymphocytes is an important new strategy in immunotherapy of cancer. One can currently isolate naturally refined, high affinity specificities from antibodies and T-cell receptors (TCRs) to use in engineered applications. We have developed two new molecules that have specificity for the overexpressed tumor antigen HER2/neu. The specificity derived from an anti-HER2 antibody variable fragment was used to create a single chain Fv (scFv). A HER2 reactive TCR was also used to develop a single chain TCR (scTCR). The HER2 binding elements were linked to an intracellular signaling module, active only in the T cell signaling pathway, providing a novel molecule to retarget lymphocytes. We demonstrate here that these molecules can be expressed in several cell lines as well as in hematopoietic stem cells (HSCs). In a transplant setting, these new receptors can be expressed in multiple cells types derived from repopulating HSCs. These new chimeric receptors will be valuable tools for further research of immune function of retargeted hematopoietic cells.

AB - The retargeting of lymphocytes is an important new strategy in immunotherapy of cancer. One can currently isolate naturally refined, high affinity specificities from antibodies and T-cell receptors (TCRs) to use in engineered applications. We have developed two new molecules that have specificity for the overexpressed tumor antigen HER2/neu. The specificity derived from an anti-HER2 antibody variable fragment was used to create a single chain Fv (scFv). A HER2 reactive TCR was also used to develop a single chain TCR (scTCR). The HER2 binding elements were linked to an intracellular signaling module, active only in the T cell signaling pathway, providing a novel molecule to retarget lymphocytes. We demonstrate here that these molecules can be expressed in several cell lines as well as in hematopoietic stem cells (HSCs). In a transplant setting, these new receptors can be expressed in multiple cells types derived from repopulating HSCs. These new chimeric receptors will be valuable tools for further research of immune function of retargeted hematopoietic cells.

KW - Cancer

KW - Chimeric antigen receptor

KW - HER2

KW - Immunotherapy

KW - Stem cell

UR - http://www.scopus.com/inward/record.url?scp=70349189946&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70349189946&partnerID=8YFLogxK

M3 - Article

VL - 8

SP - 53

EP - 63

JO - Journal of Experimental Therapeutics and Oncology

JF - Journal of Experimental Therapeutics and Oncology

SN - 1359-4117

IS - 1

ER -