Trends in cell medicine: from autologous cells to allogeneic universal-use cells for adoptive T-cell therapies

Abstract

In currently ongoing adoptive T cell therapies, T cells collected from patients are given back to them after ex-vivo activation and expansion. In some cases, T cells are transduced with chimeric antigen receptor (CAR) or T cell receptor (TCR) genes during the ex-vivo culture period in order to endow T cells with the desired antigen specificity. Although such strategies have been shown to be effective in some types of cancer, there remain issues to be solved: (i) the limited number of cells, (ii) it is time-consuming, (iii) it is costly, and (iv) the quality can be unstable. Points (ii) and (iv) can be solved by preparing allogeneic T cells and cryopreserving them in advance, and methods using healthy donor-derived T cells or pluripotent stem cells as materials are being developed. Whereas it is difficult to solve (i) and (iii) in the former case, all the issues can be cleared in the latter case. However, in either case, a new problem arises: rejection by the patient's immune system. Deletion of HLA avoids rejection by recipient T cells, but causes rejection by NK cells, which can recognize loss of HLA class I. Various countermeasures have been developed, but no definitive solution is yet available, and further research and development are necessary.