Control of leukemia relapse after allogeneic hematopoietic stem cell transplantation: integrating transplantation with genetically modified T cell therapies.|
Leukemia relapse remains a significant cause of failure after allogeneic hematopoietic stem cell transplantation (HSCT). Although it is widely accepted that immunological components of the stem cell graft play a critical role in promoting leukemia eradication (graft versus leukemia effect), it is also evident that their efficacy is frequently inadequate and leukemia relapse still occurs. This article reviews recent insights into T cell-based posttransplant immunotherapy approaches aimed at preventing or controlling leukemia relapse. Donor lymphocyte infusion with T cells genetically modified with safety switches improves the patient's immune reconstitution while offering appropriate control of graft versus host disease. T lymphocytes engineered with artificial tumor-specific receptors such as αβ T-cell receptor chains or chimeric antigen receptors are major players in promoting antileukemia effects after allogeneic HSCT. The landscape of adoptive T cell therapies after allogeneic HSCT has seen significant achievements with the introduction of T cell engineering. Gene transfer grants the generation of T cell products characterized by standardizable specificity and functionality. This aspect is critical for scalable and reproducible approaches for application in large clinical studies. The clinical results so far reported are encouraging and multicenter studies conducted by pharmaceutical companies will provide definitive conclusions on the clinical impact of these new methodologies.