State-of-Art of Cellular Therapy for Acute Leukemia

Abstract

With recent clinical breakthroughs, immunotherapy has become the fourth pillar of cancer treatment. Particularly, immune cell-based therapies have been envisioned as a promising treatment option with curative potential for leukemia patients. Hence, an increasing number of preclinical and clinical studies focus on various approaches of immune cell-based therapy for treatment of acute leukemia (AL). However, the use of different immune cell lineages and subsets against different types of leukemia and patient disease statuses challenge the interpretation of the clinical applicability and outcome of immune cell-based therapies. This review aims to provide an overview on recent approaches using various immune cell-based therapies against acute B-, T-, and myeloid leukemias. Further, the apparent limitations observed and potential approaches to overcome these limitations are discussed.

Enhancing Therapeutic Efficacy of Double Negative T Cells against Acute Myeloid Leukemia Using Idelalisib

“…AML is the most common form of adult acute leukemia with a poor overall 5-year survival rate of 30-45% for patients 60 years old or younger and 10-15% for elderly patients over 60 years of age [1,2]. Although induction chemotherapy is effective, high relapse rate and refractory disease contribute to the poor patient outcome.…”

“…Although induction chemotherapy is effective, high relapse rate and refractory disease contribute to the poor patient outcome. Currently, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only form of treatment with sustained curative potential for chemotherapy-resistant AML patients, where the treatment effect is largely driven by the graft-versus-leukemia (GvL) activity of donorderived immune cells [1]. However, severe transplant-associated toxicities, such as graftversus-host disease (GvHD), hinder its clinical benefit for patients [3].…”

“…However, only small cohorts of patients were treated with CAR-T cells, and, while effective, severe treatment-associated toxicities were observed [4][5][6][7]. In contrast, NK cell therapy was shown to be safe in multiple trials, but its clinical benefit was variable and largely confined as a consolidation therapy to prevent disease relapse, rather than to treat relapsed or refractory patients [1,8,9]. Additionally, high treatment-associated costs and difficulties in large scale manufacturing as well as poor persistence are some of the known logistical challenges of CAR-T and NK therapies, respectively [1,7].…”

“…In contrast, NK cell therapy was shown to be safe in multiple trials, but its clinical benefit was variable and largely confined as a consolidation therapy to prevent disease relapse, rather than to treat relapsed or refractory patients [1,8,9]. Additionally, high treatment-associated costs and difficulties in large scale manufacturing as well as poor persistence are some of the known logistical challenges of CAR-T and NK therapies, respectively [1,7]. Double negative T cells (DNTs) are a rare subset of mature peripheral T lymphocytes that expresses CD3 in the absence CD4 and CD8 expression.…”

Tamoxifen Sensitizes Acute Lymphoblastic Leukemia Cells to Cannabidiol by Targeting Cyclophilin-D and Altering Mitochondrial Ca2+ Homeostasis

“…In this context, multiple mechanisms of chemoresistance have been identified by which T-ALL survives after therapy, thus contributing to the frequent relapses and subsequent death of patients [4][5][6][7]. Despite the substantial progress made in antileukemic treatment [3,8,9], new strategies are needed to improve the therapy. There is accumulated evidence that a multitargeted therapy greatly improves the success rate as compared to monotherapies.…”