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- Title
A phage display selected Fab fragment with MHC class I-restricted specificity for MAGE-A1 allows for retargeting of primary human T lymphocytes.
- Authors
Willemsen, RA; Debets, R; Hart, E; Hoogenboom, HR; Bolhuis, RLH; Chames, P
- 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(ε)Rl-γ 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-A1[sup POS] 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
T cells; CANCER; CELL-mediated cytotoxicity
- Publication
Gene Therapy, 2001, Vol 8, Issue 21, p1601
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3301570