T-cell and natural killer cell therapies for hematologic malignancies after hematopoietic stem cell transplantation: enhancing the graft-versus-leukemia effect

Abstract

Hematopoietic stem cell transplantation has revolutionized the treatment of hematologic malignancies, but infection, graft-versus-host disease and relapse are still important problems. Calcineurin inhibitors, T-cell depletion strategies, and immunomodulators have helped to prevent graft-versus-host disease, but have a negative impact on the graft-versus-leukemia effect. T cells and natural killer cells are both thought to be important in the graft-versus-leukemia effect, and both cell types are amenable to ex vivo manipulation and clinical manufacture, making them versatile immunotherapeutics. We provide an overview of these immunotherapeutic strategies following hematopoietic stem cell transplantation, with discussions centered on natural killer and T-cell biology. We discuss the contributions of each cell type to graft-versus-leukemia effects, as well as the current research directions in the field as related to adoptive cell therapy after hematopoietic stem cell transplantation. ABSTRACT

'Trained immunity: consequences for lymphoid malignancies

“…The adoptive transfer of ex vivo generated autologous and allogeneic NK cells is being explored for immunotherapy in the setting of lymphoid malignancies. 85,86 Interestingly, considerable evidence exists for a close relationship between CMV infection post SCT and relapse of AML, in which NK cells are deemed to be the effectors. Moreover, CMV infection results in a mature phenotype of NK cells which also have memorylike features.…”

The Importance of Positive Immunomagnetic Cell Separation Prior to Autologous Hematopoetic Stem Cell Transplantation for Advanced Stage Lymphomas

“…multiple myeloma) can be used for consolidation post-autologous transplantation, and the allotransplantation may not be necessarily performed, taking in consideration the very high morbidity and mortality of the procedure. 9 Immunogenetic CD34+ cell selection has been introduced in the Hematology Clinic and Bone Marrow Transplantation Unit of Tîrgu Mureș with the aim to purify the graft to prevent relapse and to enhance a durable engraftment in stage IV non-Hodgkin lymphomas. 10,11 The results obtained by this method are comparable with the results from very experienced transplant centers.…”

Personalized medicine in adult acute lymphoblastic leukemia

“…Another promising new approach is chimeric antigen receptor modified T cells, targeting CD19 + B-lineage ALL cells. 27 When these genetically engineered T cells were given to children with refractory/ relapsed ALL, the complete remission rate was 90%, with an event-free survival of 63% at 6 months, and an overall survival of 78%.…”