Genetic modificated, with chimeric antigen receptor, T lymphocytes therapies in hematological malignancies

Haema 2016; 7(1): 27-36

by Panagiotis Kaloyannidis

Haematology Clinic – Bone Marrow Transplantation Unit, Gene and Cell Therapy Center “G. Papanikolaou” General Hospital, Thessaloniki, Greece

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Current chemotherapy protocols, hematopoietic stem cell transplantation and support- ive care have led to remarkable improvements in the outcome of patients with hematologic malignancies. However, therapeutic approaches of high efficacy and low toxicity remain a highly desirable, albeit challenging goal in hematology and oncology in general. In this context, cellular-based therapies have enormous capabilities. The knowledge that donor lymphocyte infusions have the potential to eradicate relapsed disease following allogeneic hematopoietic stem cell transplantation, provided the conceptual basis of the effort to generate T lymphocytes with specific activity against tumor cells. The genetic modification of T-cells to express an additional to their native TCR, chimeric antigen receptor- (CAR-), combines the HLA-independent binding of cell surface target molecules with the delivery of a tailored activating signal to the engineered immune cells, with the goal to deliver effective anti-tumor activity and long term persistence. Engineered CARs are incorporated into peripheral blood T cells by using various vector transfer systems, most commonly integrating viral vectors. The B-cell origin antigens are the most widely used surface antigen targets. CAR/T-cell-based immunotherapy has been under development for almost 20 years, over which period it has progressed from a novel and complex technology to an emerging alternative therapeutic modality for hematological malignant diseases. However, sever- al issues in terms of safety and efficacy still remain to be addressed. This brief review summarizes the most recent biological and clinical developments and highlights the future directions towards the wide application of cellular therapies in hematological malignancies.