Relapsing or persistent acute myeloid leukemia (AML) represents a severe form of
cancer that is difficult to treat and has a grim outlook. The necessity for innovative treatments is evident due to the scarcity of effective options. The conventional production of CAR-T cells is a time-consuming and costly process that involves significant ex vivo cell expansion after viral transduction, which is not ideal for patients who require prompt treatment.
The UltraCAR-T platform is a novel approach that aims to overcome these challenges by offering a quicker, more local manufacturing process that can be executed in a hospital's GMP-compliant facility immediately after patient apheresis. This platform uses
Precigen's cutting-edge non-viral multi-gene delivery system and maintains high cell viability, enabling the rapid delivery of autologous CAR-T cells just one day post gene transfer.
The PRGN-3006 UltraCAR-T cells, developed using Precigen's UltraVector platform, are engineered to express
CD33 CAR, membrane-bound
IL-15 (mbIL15), and a kill switch. The inclusion of mbIL15 provides the cells with an internal cytokine source, enhancing their expansion and longevity in the presence of tumor antigens without the need for additional cytokines. This feature also negates the requirement for T cell expansion before administration. The kill switch co-expression offers a method for controlled elimination of the cells post-treatment, enhancing safety and therapeutic control.
The PRGN-3006 UltraCAR-T cells were successfully manufactured using a non-viral gene transfer method and a streamlined production process from various donor T cells. Flow cytometry and western blot analyses confirmed the co-expression of the CAR, mbIL15, and kill switch. In vitro tests showed robust expansion in the presence of the CD33 antigen, no autonomous expansion without CD33, and sustained persistence without exogenous cytokines. The cells demonstrated specific killing of CD33+ tumor cells and released significant levels of inflammatory cytokines like
IFNγ when co-cultured with
AML tumor cells. The kill switch activator antibody was also shown to specifically eliminate PRGN-3006 cells.
In an in vivo aggressive AML xenograft model using immunocompromised mice, a single administration of
PRGN-3006 UltraCAR-T cells, given just one day after gene transfer, effectively reduced tumor burden and significantly improved survival rates compared to conventional CAR-T cells lacking mbIL15 expression (p<0.01). The PRGN-3006 cells showed better engraftment, expansion, and persistence in the mice.
The promising pre-clinical results support the initiation of clinical trials for PRGN-3006 UltraCAR-T in treating AML. The FDA has granted approval for an investigational new drug application, and a Phase 1 clinical trial for patients with
relapsed/refractory AML and
high-risk myelodysplastic syndrome is underway (ClinicalTrials.gov Identifier: NCT03927261).
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.
