The Hematology of Tomorrow Is Here-Preclinical Models Are Not: Cell Therapy for Hematological Malignancies.

Abstract

Simple SummaryCell therapy is revolutionizing the prospect of deadly hematological malignancies such as high-risk acute myeloid leukemia. Stem cell therapy of allogeneic source from compatible human leukocyte antigen donor has exceptional success promoting durable remissions, but the rate of relapse is currently still high and there is transplant-related mortality. This review presents the current knowledge on the clinical use of mesenchymal stromal cells to improve outcomes in hematopoietic stem cell transplants. As an alternative or adjuvant approach to prevent relapse, we summarize the status of the promising forms of cellular immunotherapy aimed at targeting not only the bulk but also the cells of origin of leukemia. Finally, we discuss the available in vivo models for disease modelling and treatment efficacy prediction in these contexts.The purpose of this review is to present the current knowledge on the clinical use of several forms of cell therapy in hematological malignancies and the preclinical models available for their study. In the context of allogeneic hematopoietic stem cell transplants, mesenchymal stromal cells are pursued to help stem cell engraftment and expansion, and control graft versus host disease. We further summarize the status of promising forms of cellular immunotherapy including CAR T cell and CAR NK cell therapy aimed at eradicating the cells of origin of leukemia, i.e., leukemia stem cells. Updates on other forms of cellular immunotherapy, such as NK cells, CIK cells and CAR CIK cells, show encouraging results in AML. The considerations in available in vivo models for disease modelling and treatment efficacy prediction are discussed, with a particular focus on their strengths and weaknesses for the study of healthy and diseased hematopoietic stem cell reconstitution, graft versus host disease and immunotherapy. Despite current limitations, cell therapy is a rapidly evolving field that holds the promise of improved cure rates, soon. As a result, we may be witnessing the birth of the hematology of tomorrow. To further support its development, improved preclinical models including humanized microenvironments in mice are urgently needed.