Individuals battling
relapsed acute myeloid leukemia face a grim outlook with few therapeutic avenues. CAR T cell technology has shown remarkable success in treating
blood cancers, offering long-lasting remissions to patients who have undergone extensive prior treatments. The exploration of T cell-based immunotherapies that target
AML cells is a promising field, with the potential for curing the disease. However, creating personalized CAR T therapies for AML poses logistical hurdles and clinical challenges due to the rapid progression of the disease and the difficulty in obtaining a sufficient quantity of healthy T cells from AML patients. An off-the-shelf CAR T cell product could be advantageous in such cases.
The study described involves a preclinical assessment of ALLO-819, an allogenic CAR T therapy that targets the
Flt3 receptor tyrosine kinase, a prevalent AML marker with minimal expression outside of blood-forming tissues. A Flt3 CAR was engineered using a range of high-affinity, fully-human antibodies identified through phage display technology. These antibodies were incorporated into CAR constructs to redirect T cells towards AML cells, with a focus on minimizing unwanted signaling and enhancing antitumor capabilities. The lead CAR was further modified to include a safety mechanism that could be activated by
rituximab, an FDA-approved antibody, to control CAR T cell activity.
The allogenic ALLO-819 Flt3 CAR T cells were designed to mitigate the risk of
graft-versus-host disease and to be resistant to lysis by anti-
CD52 antibodies, using gene-editing techniques to disrupt specific genetic loci. These cells demonstrated target-specific activation and potent antitumor effects when co-cultured with AML cells.
While Flt3 expression was detected on some normal hematopoietic stem and progenitor cells, which were susceptible to CAR T cell cytotoxicity, the off-
tumor effects were limited and associated with antitumor efficacy. The administration of rituximab effectively depleted CAR T cells, allowing for the rapid recovery of normal stem cells.
The findings of the study endorse the potential of ALLO-819 Flt3 CAR T as an innovative treatment for AML. The disclosures section lists affiliations and interests of the authors, including employment, equity ownership, and patents related to
Allogene Therapeutics,
Pfizer Inc., and
Cellectis Inc.How to Use Synapse Database to Search and Analyze Translational Medicine Data?
The transational medicine section of the Synapse database supports searches based on fields such as drug, target, and indication, covering the T0-T3 stages of translation. Additionally, it offers a historical conference search function as well as filtering options, view modes, translation services, and highlights summaries, providing you with a unique search experience.

Taking obesity as an example, select "obesity" under the indication category and click search to enter the Translational Medicine results list page. By clicking on the title, you can directly navigate to the original page.

By clicking the analysis button, you can observe that GLP-1R treatment for obesity has gained significant attention over the past three years, with preclinical research still ongoing in 2023. Additionally, there are emerging potential targets, such as GDF15, among others.

Click on the image below to go directly to the Translational Medicine search interface.
