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Antigen-dependent CD28 Signaling Selectively Enhances Survival and Proliferation in Genetically Modified Activated Human Primary T Lymphocytes
- Source :
- The Journal of Experimental Medicine
- Publication Year :
- 1998
- Publisher :
- Rockefeller University Press, 1998.
-
Abstract
- Most tumor cells function poorly as antigen-presenting cells in part because they do not express costimulatory molecules. To provide costimulation to T lymphocytes that recognize tumor cells, we constructed a CD28-like receptor specific for GD2, a ganglioside overexpressed on the surface of neuroblastoma, small-cell lung carcinoma, melanoma, and other human tumors. Recognition of GD2 was provided by a single-chain antibody derived from the GD2-specific monoclonal antibody 3G6. We demonstrate that the chimeric receptor 3G6-CD28 provides CD28 signaling upon specific recognition of the GD2 antigen on tumor cells. Human primary T lymphocytes retrovirally transduced with 3G6-CD28 secrete interleukin 2, survive proapoptotic culture conditions, and selectively undergo clonal expansion in the presence of an antiidiotypic antibody specific for 3G6-CD28. Polyclonal CD8+ lymphocytes expressing 3G6-CD28 are selectively expanded when cultured with cells expressing allogeneic major histocompatibility complex class I together with GD2. Primary T cells given such an antigen-dependent survival advantage should be very useful to augment immune responses against tumor cells.
- Subjects :
- Interleukin 2
CD3 Complex
Cell Survival
Recombinant Fusion Proteins
T-Lymphocytes
Immunology
Apoptosis
Lymphocyte Activation
Major histocompatibility complex
Mice
CD28 Antigens
Antigen
Gangliosides
medicine
Animals
Humans
Immunology and Allergy
IL-2 receptor
gene transfer
Cells, Cultured
chimeric receptors
Lymphokine-activated killer cell
ganglioside
biology
Histocompatibility Antigens Class II
CD28
Receptors, Interleukin-2
adoptive cell therapy
Articles
Molecular biology
Antibodies, Anti-Idiotypic
costimulation
Interleukin 12
biology.protein
Cancer research
Interleukin-2
Peptides
Cell Division
CD8
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 15409538 and 00221007
- Volume :
- 188
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental Medicine
- Accession number :
- edsair.doi.dedup.....c2ef59d43b8cbdd8e089d15a60a7e71f
- Full Text :
- https://doi.org/10.1084/jem.188.4.619