Development of Augmented Leukemia/Lymphoma-Specific T-Cell Immunotherapy for Deployment with Haploidentical Hematopoietic Progenitor-Cell Transplant.

摘要

This project develops novel immune-based therapies to target childhood leukemia. By combining gene therapy with T-cell therapy we have developed new biologic agents that specifically recognize CD19 molecule on the cell surface of B-cell acute lymphoblastic leukemia (B-ALL). To translate this approach to the clinic we have adapted the Sleeping Beauty (SB) transposon/transposase system to express a CD19-specific chimeric antigen receptor (CAR). T cells that have undergone transposition express the CAR and therefore redirected specificity for CD19. To selectively propagate CD19-specific T cells to clinically-meaningful numbers we have developed artificial antigen presenting cells (aAPC) by expressing CD19 molecule and desired co-stimulatory molecules on K562 cells. Thus, by combining SB transposition and aAPC, we can harness gene therapy and T-cell therapy to develop targeted treatment for B-ALL.