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MAGE-A3 TCR-engineered T cells
- Development stage
- Discontinued
- Lead developer
- National Cancer Institute
- Modality
- TCR-Engineered T Cells → Engineered T Cells → Adoptive Cell Transfer → Cell Therapies, Gene Therapies
- Administration
- Intravenous
01
Overview
MAGE-A3 TCR-engineered T cells are an experimental adoptive cell therapy consisting of autologous T cells genetically modified to express an affinity-enhanced T-cell receptor (TCR) targeting the MAGE-A3 cancer-testis antigen. Developed by the National Cancer Institute (NCI) in collaboration with the University of Pennsylvania and Washington University, the therapy was designed to treat HLA-A*01 or HLA-A*02 positive patients with MAGE-A3-expressing tumors such as melanoma and multiple myeloma. Clinical development was halted after trials (NCT01350401, NCT01352286) revealed fatal toxicities. Specifically, the HLA-A*01-restricted TCR (a3a) caused lethal cardiogenic shock due to unexpected cross-reactivity with a peptide from the cardiac muscle protein titin, while the HLA-A*02-restricted version was associated with fatal neurological toxicity.
- Other names
- MAGE-A3-specific TCR-engineered T cellsMAGE-A-3-specific TCR-engineered T cellsMAGE-A 3-specific TCR-engineered T cellsanti-MAGE-A3 TCR T cellsanti-MAGE-A-3 TCR T cellsanti-MAGE-A 3 TCR T cells
02
Targets
MAGE-A3/HLA-DPB1*04:01 (Melanoma-associated antigen 3 peptide presented by Human Leukocyte Antigen DPB1*04:01)
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