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Re-examination of MAGE-A3 as a T-cell Therapeutic Target
- Source :
- Journal of Immunotherapy; 20240101, Issue: Preprints
- Publication Year :
- 2024
-
Abstract
- Supplemental Digital Content is available in the text.In 2013, an innovative MAGE-A3-directed cancer therapeutic of great potential value was terminated in the clinic because of neurotoxicity. The safety problems were hypothesized to originate from off-target T-cell receptor activity against a closely related MAGE-A12 peptide. A combination of published and new data led us to test this hypothesis with current technology. Our results call into question MAGE-A12 as the source of the neurotoxicity. Rather, the data imply that an alternative related peptide from EPS8L2 may be responsible. Given the qualities of MAGE-A3 as an onco-testis antigen widely expressed in tumors and largely absent from normal adult tissues, these findings suggest that MAGE-A3 may deserve further consideration as a cancer target. As a step in this direction, the authors isolated 2 MAGE-A3 peptide-major histocompatibility complex-directed chimeric antigen receptors, 1 targeting the same peptide as the clinical T-cell receptor. Both chimeric antigen receptors have improved selectivity over the EPS8L2 peptide that represents a significant risk for MAGE-A3-targeted therapeutics, showing that there may be other options for MAGE-A3 cell therapy.
Details
- Language :
- English
- ISSN :
- 15249557
- Issue :
- Preprints
- Database :
- Supplemental Index
- Journal :
- Journal of Immunotherapy
- Publication Type :
- Periodical
- Accession number :
- ejs54862049
- Full Text :
- https://doi.org/10.1097/CJI.0000000000000348