SUMMARY
UCLA researchers in the Department of Pathology and Medicine have developed human stem cells that can be used to generate non-alloreactive, antigen specific T cells for adoptive cell therapy.
BACKGROUND
Adoptive cell therapy (ACT) with engineered T cells has shown unprecedented potential in the treatment of cancer, infectious diseases, and other conditions. One of the major limitations of current engineered T cell therapies is the requirement of autologous T cells as the cellular vehicle to prevent potential tissue damage from alloreactivity of donor T cells to HLA-mismatched recipients. This requirement for autologous T cell collection increases the cost and manufacturing logistics of these therapies and in some cases may exclude patient populations who lack sufficient T cells. The development of safe “universal” or “off-the shelf” allogeneic T cell therapies is therefore a high priority for the field of immunotherapy.
INNOVATION
The inventors have developed human stem cells (including hematopoietic stem cells and pluripotent stem cells) that lack the expression of the genes RAG1 and/or RAG2, which, in combination with an introduced antigen specific receptor sequence and in vitro differentiation to effector T cells, can be used to generate non-alloreactive, antigen specific T cells for adoptive cell therapy for cancer and other diseases.
APPLICATIONS
- Treatment of cancer and infectious diseases
- Adoptive cell therapy
ADVANTAGES
- Universal donor - lack of endogenous TCR expression and alloreactivity
- No development of bystander T cells from RAG-disrupted stem cells that lack expression of the desired antigen specific TCR
- No risk of RAG re-expression in mature T cells
RELATED MATERIALS
Seet, C.S., He, C., Bethune, M.T., Li, S., Chick, B., Gschweng, E.H., Zhu, Y., Kim, K., Kohn, D.B., Baltimore, D. and Crooks, G.M., Generation of mature T cells from human hematopoietic stem and progenitor cells in artificial thymic organoids, Nature Methods, 2017.