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A phage display selected fab fragment with MHC class I-restricted specificity for MAGE-A1 allows for retargeting of primary human T lymphocytes.
- Source :
-
Gene therapy [Gene Ther] 2001 Nov; Vol. 8 (21), pp. 1601-8. - Publication Year :
- 2001
-
Abstract
- The clinical benefit of adoptive transfer of MHC-restricted cytotoxic T lymphocytes(CTL) for the treatment of cancer is hampered by the low success rate to generate antitumor CTLs. To bypass the need for tumor-specific CTL, we developed a strategy that allows for grafting of human T lymphocytes with MHC-restricted antigen specificity using in vitro selected human Fab fragments fused to the Fc(epsilon)RI-gamma signaling molecule. Retroviral introduction of a Fab-based chimeric receptor specific for MAGE-A1/HLA-A1 into primary human T lymphocytes resulted in binding of relevant peptide/MHC complexes. Transduced T lymphocytes responded to native MAGE-A1/HLA-A1POS target cells by specific cytokine production and cytolysis. Therefore, peptide/MHC-specific Fab fragments represent new alternatives to TCR to confer human T lymphocytes with tumor specificity, which provides a promising rationale for developing immunogene therapies.
- Subjects :
- Antigens, Neoplasm
Epitopes
Genetic Vectors administration & dosage
HLA-A1 Antigen immunology
Humans
Immunoglobulin Fab Fragments metabolism
Melanoma immunology
Melanoma-Specific Antigens
Neoplasm Proteins immunology
Peptide Library
Retroviridae genetics
T-Lymphocytes, Cytotoxic immunology
Transduction, Genetic
Tumor Cells, Cultured
Genetic Therapy methods
Immunoglobulin Fab Fragments genetics
Immunotherapy, Adoptive methods
Melanoma therapy
Receptors, Immunologic genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0969-7128
- Volume :
- 8
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Gene therapy
- Publication Type :
- Academic Journal
- Accession number :
- 11894998
- Full Text :
- https://doi.org/10.1038/sj.gt.3301570