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 (TAA) are being identified, enabling for engineering 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. (Xiangxue Pharmaceutical), 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 than enhance the affinity of the TCR to optimize tumor recognition and killing. High affinity TCRs (HAT) generated in this manner can then be used to treat cancer by either generating tumor specific TCR-engineered T cells (TCR-T) from a patient’s own cells or by engaging and directing endogenous T cells to target and kill cancer cells through the use of high-affinity soluble TCR (HATac). The addition of a T cell based immunotherapy platform to our existing pipeline of therapeutic technologies represents our commitment to improving outcomes in the greatest number of patients worldwide.