Journal Article Ppublish 1 citation
PubMed: 39624992 DOI: 10.1158/2643-3230.BCD-23-0258
CD33-CD123 IF-THEN Gating Reduces Toxicity while Enhancing the Specificity and Memory Phenotype of AML-Targeting CAR-T Cells.
Blood Cancer Discov 6(1):55-72
Authors: Samy Jambon, Jianping Sun, Shawn Barman, Sakunthala Muthugounder, Xue Rachel Bito, Armita Shadfar, Alexandra E Kovach, Brent L Wood, Varsha Thoppey Manoharan, A Sorana Morrissy, Deepa Bhojwani, Alan S Wayne, Michael A Pulsipher, Yong-Mi Kim, Shahab Asgharzadeh, Chintan Parekh, Babak Moghimi
Affiliations
- Division of Hematology and Oncology, Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California.
- Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California.
- Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Canada.
- Division of Hematology and Oncology, Primary Children's Hospital, Huntsman Cancer Institute, Spencer Fox Eccles School of Medicine at the University of Utah, Salt Lake City, Utah.
Abstract
Our study demonstrates the use of "IF-THEN" SynNotch-gated CAR-T cells targeting CD33 and CD123 in AML reduces off-tumor toxicity. This strategy enhances T-cell phenotype, improves expansion, preserves HSPCs, and mitigates cytokine release syndrome-addressing critical limitations of existing AML CAR-T therapies.
MeSH
Cells, Neoplasms, Phenotype, Therapeutics, Memory, Car-T Cell