The past 10 years have seen tremendous progress in the field of immunotherapy, particularly in the area of T-cell therapies. This approach is exemplified by engineered T-cells bearing an artificial Chimeric Antigen Receptor (CAR) that recognizes a specific protein expressed on the surface of tumor cells leading to rapid activation and tumor cell killing. While clinical success has been achieved in a small number of tumor types, the repertoire of surface proteins available for targeting with this technology is limited, severely restricting the development of CAR-T cells for multiple tumor types. In addition, the surface proteins targeted to date are also expressed on normal cells, resulting in CAR-T-mediated killing of non-cancerous cells and potentially life threatening side effects related to the magnitude of the ensuing immune response.
To address the scope and selectivity issues of CAR-T, Athenex is developing T-Cell Receptor Engineered T-Cell (TCR-T) based approaches. A TCR’s ability to selectively recognize target cells comes from its unique capacity to recognize “antigens” on the surface of cells. These antigens can be selective identifiers of malignant cells and a growing number of tumor associated antigens are being identified, enabling the engineering of a potent and selective TCR-T directed response against cancer.
Athenex has established a joint venture with Xiangxue Life Sciences, a wholly-owned subsidiary of Guangzhou Xiangxue Pharmaceutical Co., Ltd., to develop cell-based therapies that take advantage of the unique attributes of TCR mediated target recognition. Central to this platform is the ability to first identify endogenous TCRs with specificity for a defined tumor antigen and to then enhance the affinity of the TCR to optimize tumor recognition and killing. These High Affinity TCRs can be incorporated into a patient’s own T-cells converting the cells into a potent anti-cancer therapy. Using this technology, we believe the platform has generated engineered T-cells with higher binding affinity, specificity for intended target cells, expression level of the TCR and persistence in patients’ circulation during therapy. Preliminary studies have shown positive clinical signals.