Instead of designing T cells to fight cancer, an MIT group is using synthetic biology to directly manipulate the tumor cells and make them more immunogenic. The big advantage, says the team, is that the system uses intracellular cues to trigger tumor-specific immunity rather than cell-surface antigens, vastly expanding the toolbox for limiting off-target toxicity.
The findings have been licensed by Senti Biosciences Inc., a synthetic biology startup spun out of the Massachusetts Institute of Technology (MIT) last year by Timothy Lu, principal investigator on the new study.
Lu is an associate professor of biological engineering, electrical engineering and computer science at the institute.
The first generation of cell therapies in immuno-oncology uses individual synthetic proteins like chimeric antigen receptors (CARs) to recognize extracellular tumor antigens and kill cells that display them on their surfaces. The technology has achieved clinical validation with the approval of Kite Pharma Inc.’s Yescarta axicabtagene ciloleucel and Novartis AG’s Kymriah tisagenlecleucel. Kite was acquired by Gilead Sciences Inc. in October.
So far, engineered cellular immunotherapies have only made significant ground in hematological cancers, where they target cell surface antigens shared by malignant and normal B cells. While losing normal B cells is an acceptable side effect,