Development history of TCR-T cell therapy

In 2002, Rosenberg's team was the first to discover that tumor-infiltrating lymphocytes (TILs) isolated from melanoma can specifically kill tumor cells when amplified and transfused in vitro. However, in other tumors, TILs are often difficult to obtain and take a long time to expand in vitro. Most of them are terminal differentiated T cells after expansion, and the sustained anti-tumor effect is weak. In this context, people are exploring whether the known antigen-specific TCR gene can be introduced into normal peripheral blood lymphocytes (PBL) for treatment, which is TCR-T cell therapy. 

In the development process of TCR-T technology, four iterations have been experienced:

The first generation of TCR-T was isolated from T cells of patients with tumor antigen specific recognition of T cell subsets, expanded in vitro and then transfused back for treatment. Because of the small number of T cell clones and large individual differences, it is difficult to industrialize.

The second generation of TCR-T is to clone the T cells specifically recognized by the above tumor antigen, obtain the TCR gene sequence, and then transfer it to the peripheral T cells of patients. This method makes the industrialization of TCR-T possible.

The third generation of TCR-T is to improve the druggability of TCR-T by optimizing the affinity of TCR, making it better able to recognize tumor antigens, and then transducing it to patient T cells.

The fourth-generation TCR-T is a highly specific cell therapy targeting tumor neoantigens, with significantly improved tumor response and safety.

What is TCR-T cell therapy

TCR-T cell therapy, short for T cell receptor-engineered T cells, is based on gene editing technology to specifically recognize tumor antigen T cell receptors（TCR ）gene, be introduced into the patient's own T cells to make them express exogenous TCR, so as to recognize and attack tumor cells and achieve the purpose of tumor treatment.