Chimeric Antigen Receptor Therapy in Acute Lymphoblastic Leukemia Clinical Practice

Abstract

Over half of patients diagnosed with B-cell acute lymphoblastic leukemia (ALL) develop relapsed or refractory disease. Traditional chemotherapy salvage is inadequate, and new therapies are needed. Chimeric antigen receptor (CAR) T cell therapy is a novel, immunologic approach where T cells are genetically engineered to express a CAR conferring specificity against a target cell surface antigen, most commonly the pan-B-cell marker CD19. After infusion, CAR T cells expand and persist, allowing ongoing tumor surveillance. Several anti-CD19 CAR T cell constructs have induced high response rates in heavily pre-treated populations, although durability of response varied. Severe toxicity (cytokine release syndrome and neurotoxicity) is the primary constraint to broad implementation of CAR T cell therapy. Here, we review the experience of CAR T cell therapy for ALL and ongoing efforts to modify existing technology to improve efficacy and decrease toxicity. As an anti-CD19 CAR T cell construct may be FDA approved soon, we focus on issues relevant to practicing clinicians.

Therapy of Relapsed/ Refractory Acute Lymphoblastic Leukemia Today and Tomorrow

“…Na povrchu lymfoblastů je několik antigenů, které lze rotoxicita, deplece zdravých B lymfocytů s hypogamaglobulinemií a infekční komplikace. Výsledky léčby jsou ale i přes vysokou toxicitu motivující, již několik na sobě nezávislých studií fáze I a II prokázalo > 90 % navozených CR u dětských i dospělých pacientů s R/ R ALL [22][23][24].…”

Chimeric Antigen Receptor T-Cells for the Treatment of B-Cell Acute Lymphoblastic Leukemia

“…One of the first documented adverse effects of CAR-T in clinical use is the CRS and B-cell aplasia ( 38 – 42 ). CRS is caused mainly by the expansion of the infused T-cells ( 43 ), but other cells including B, T, and natural killer (NK) cells, and myeloid cells such as dendritic cells, monocytes, and macrophages seems to contribute to the development of CRS.…”

The future of immune checkpoint blockade immunotherapy: towards personalized therapy or towards combination therapy

“…Chimeric antigen receptors (CARs) are membrane-bound synthetic receptors on T and NK (CAR-T and NK) cells to target cancer cell-surface antigens and augment T and NK function. CAR-T and NK cell therapy has been evaluated in hematological malignancies in clinical trials and in approved clinical applications (12) and is also being translated into solid cancers (13). This strategy will not only provide systemic immunity that is required for effective cancer immunotherapy (14), but may also increase local infiltration of T and NK cells in tumor microenvironment.…”