Back to Search
Start Over
Redirected primary T cells harboring a chimeric receptor require costimulation for their antigen-specific activation
- Source :
- Blood. 105:3087-3093
- Publication Year :
- 2005
- Publisher :
- American Society of Hematology, 2005.
-
Abstract
- Chimeric receptor (CR)–redirected lymphocytes (T bodies) have great potential in the eradication of tumor cells. To extend this approach to target cells that do not express surface ligands to costimulatory receptors (eg, cancer cells), we have generated an antibody-based tripartite chimeric receptor (TPCR) that contains scFv linked to the costimulatory molecule, CD28 without its ligand-binding domain, and to the cytoplasmic moiety of the FcRγ subunit. In this study, we tested the ability of 2,4,6-trinitrophenyl (TNP)–specific TPCR to drive primary, naïve T cells derived from CR-transgenic (Tg) mice to undergo full activation. As a control, we used Tg mice expressing a similar transgene but lacking the signaling region of CD28 (Tg-TPCRΔCD28). Only T cells from the TPCR-Tg and not the CD28-truncated TPCR-Tg mice could undergo activation following stimulation on hapten-modified target cells not expressing B7. Moreover, when stimulated with TNP protein displayed on plastic, the TPCR-Tg T cells expressing the entire TPCR gene became fully activated for proliferation, interleukin 2 production, protection from apoptosis, and killing of TNP-modified target cells. Finally, TPCR-Tg mice manifested a delayed-type hypersensitivity response following skin challenge in the absence of priming. Taken together, our results suggest that the TPCR is the receptor configuration of choice for clinical applications using primary T or stem cells.
- Subjects :
- Interleukin 2
Lymphoma, B-Cell
Recombinant Fusion Proteins
T-Lymphocytes
Immunology
Priming (immunology)
Apoptosis
Mice, Transgenic
chemical and pharmacologic phenomena
Biology
Lymphocyte Activation
Biochemistry
Antibodies
Mice
CD28 Antigens
Antigen
Cell Line, Tumor
Lymphocyte costimulation
medicine
Animals
T-cell receptor
Interleukin-2 Receptor alpha Subunit
CD28
Receptors, Interleukin
Cell Biology
Hematology
T lymphocyte
Molecular biology
Cancer cell
B7-1 Antigen
Interleukin-2
Immunotherapy
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 105
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....ee0ed2806b1344ef5d0cc0278daae6de