716. Durable Acute Myeloid Leukemia Remission Without Myeloablation in an Innovative Xenotolerant Mouse Model of CD44v6 CAR-T Cell Immunotherapy

Chemotherapy resistance and relapse remain significant sources of mortality for children and adults with acute myeloid leukemia (AML). Further intensification of conventional cytotoxic chemotherapy is likely not feasible due to the severity of acute and long-term side effects upon normal tissues commonly induced by these drugs. Successful development and implementation of new precision medicine treatment approaches for patients with AML, which may improve leukemia remission and diminish toxicity, is thus a major priority. Tumor antigen-redirected chimeric antigen receptor (CAR) T-cell immunotherapies have induced remarkable responses in patients with relapsed or chemorefractory B-lymphoblastic leukemia, and similar strategies are now under early clinical study in adults with relapsed/refractory AML. However, potential on target/off tumor toxicity of AML CAR T-cell immunotherapies, notably aplasia of normal myeloid cells, may limit broader implementation of such approaches. Careful selection of optimal target antigens, consideration of toxicity mitigation strategies, and development of methodologies to circumvent potential CAR T-cell resistance are essential for successful implementation of cellular immunotherapies for patients with high-risk AML.

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CARving the Path to Allogeneic CAR T Cell Therapy in Acute Myeloid Leukemia

Frontiers in Oncology ◽

10.3389/fonc.2021.800110 ◽

2022 ◽

Vol 11 ◽

Author(s):

Oren Pasvolsky ◽

May Daher ◽

Gheath Alatrash ◽

David Marin ◽

Naval Daver ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

T Cell ◽

Cell Therapy ◽

Myeloid Leukemia ◽

Disease Free Survival ◽

T Cell Therapy ◽

Car T Cell ◽

Car T Cell Therapy ◽

Car T ◽

Acute Myeloid

Despite advances in the understanding of the genetic landscape of acute myeloid leukemia (AML) and the addition of targeted biological and epigenetic therapies to the available armamentarium, achieving long-term disease-free survival remains an unmet need. Building on growing knowledge of the interactions between leukemic cells and their bone marrow microenvironment, strategies to battle AML by immunotherapy are under investigation. In the current review we describe the advances in immunotherapy for AML, with a focus on chimeric antigen receptor (CAR) T cell therapy. CARs constitute powerful immunologic modalities, with proven clinical success in B-Cell malignancies. We discuss the challenges and possible solutions for CAR T cell therapy development in AML, and examine the path currently being paved by preclinical and clinical efforts, from autologous to allogeneic products.

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Chimeric Antigen Receptor (CAR) T Cell Therapy in Acute Myeloid Leukemia (AML)

Journal of Clinical Medicine ◽

10.3390/jcm8020200 ◽

2019 ◽

Vol 8 (2) ◽

pp. 200 ◽

Cited By ~ 23

Author(s):

Susanne Hofmann ◽

Maria-Luisa Schubert ◽

Lei Wang ◽

Bailin He ◽

Brigitte Neuber ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

T Cell ◽

Cell Therapy ◽

Chimeric Antigen Receptor ◽

Myeloid Leukemia ◽

T Cell Therapy ◽

Car T Cell ◽

Car T Cell Therapy ◽

Car T ◽

Acute Myeloid

Despite high response rates after initial chemotherapy in patients with acute myeloid leukemia (AML), relapses occur frequently, resulting in a five-year-survival by <30% of the patients. Hitherto, allogeneic hemotopoietic stem cell transplantation (allo-HSCT) is the best curative treatment option in intermediate and high risk AML. It is the proof-of-concept for T cell-based immunotherapies in AML based on the graft-versus-leukemia (GvL)-effect, but it also bears the risk of graft-versus-host disease. CD19-targeting therapies employing chimeric antigen receptor (CAR) T cells are a breakthrough in cancer therapy. A similar approach for myeloid malignancies is highly desirable. This article gives an overview on the state-of-the art of preclinical and clinical studies on suitable target antigens for CAR T cell therapy in AML patients.

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