St. Jude Reference #SJ-21-0009
Cancers express splice variants since their spliceosome is altered. Using bioinformatic analysis, researchers at St. Jude have identified two splice variants of extracellular matrix proteins, tenascin C (TNC) and procollagen 11A1 (Col11A1), that are overexpressed in pediatric cancer. The researchers then developed two CARs that target these splice variants. One is based on the monoclonal antibody (MAb) G11 and recognizes the C domain of TNC (C.TNC) and the other is based on the MAb 1E8.33 and recognizes an epitope in procollagen Col11A1. T cells expressing our CAR prototypes recognize and kill C.TNC+ or Col11A1+ cancer cells in vitro. In addition, pilot in vitro experiments have demonstrated that C.TNC-CARTs or Col11A1-CARTs have significant antitumor activity.
The generated CARs can be expressed in other immune cells (for example but not limited to γδ T cells, iNKT cells, NK cells, or macrophages). Of note, C.TNC and Col11A1 are expressed not only in pediatric but also adult tumors, allowing broad applicability; such as solid and brain tumors. In addition, one concern of targeting solid tumors with CAR T cells is ‘on target/off cancer’ toxicity; C.TNC- or Col11A1-CAR T cells have the potential to reduce the risk of ‘on target/off cancer’ toxicity.
Cancer, splice variant, tenascin C (TNC), procollagen 11A1 (Col11A1), Chimeric antigen receptor, gene therapy, cell therapy, CAR, (MAb) G11, MAb 1E8.33, antitumor, solid tumor, brain tumors.
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