The past 10 years have seen tremendous progress in the field of immunotherapy, particularly in the area of adoptive 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 T cell activation and tumor cell killing. While clinical success has been achieved in hematological malignancies, the repertoire of surface proteins available for targeting with this technology is limited, severely restricting the development of CAR-T cells for solid tumors. 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 limited 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 solid tumors comes from its unique capacity to recognize “intracellular tumor-specific antigens”. An increasing number of tumor-associated antigens (TAA) are being identified, enabling the engineering of a potent and selective TCR-T directed response against multiple cancer types.
Athenex has established a joint venture with Xiangxue Life Sciences, a 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. Preclinical and early clinical findings have indicated this TCR-T cell therapy technology could potentially be an effective treatment for multiple solid tumor types.