Re-engineering CD4 T- Cells into Lineage Specifiic, Pluripotent Stem Cells (Tscm)

Categories: “Other Disorders“

Reference #: 2020-030

OTC Contact: Ruchika Nijhara, PhD, MBA, CLP; Office: (202) 687-3721 (Directory Information | Send a Message)

INVENTION

The present invention introduces a method of re-engineering CD4 T-cells to induce stem cell like memory (Tscm) functions therein. The proposed method uses MEK 1/2 inhibitors to produce CD4 memory cells with stem cell properties. The MEK 1/2 inhibition allows naïve CD4 T-cells to become amenable to lineage specific conditioning, leading to the generation of specific effectors cells upon antigenic stimulation. Thus, the invention provides a means of generating disease specific Tscm cells, with properties including; self-renewability, robust antigen specific responses and cytokine sensitive differentiation into CD4 subpopulations.

BACKROUND

T-cell therapy is a fast-growing area of interest in treatment approaches to cancer and other diseases. The current state of the art utilizes variations of in-vitro strategies to generate therapeutic T-cells, ultimately requiring the re-infusion of modified T-cells. These approaches invariably require a large number of T-cells to prove efficacious, and these cells undergo exhaustion and apoptosis.

Georgetown researchers herein advance an approach focused on re-engineering such cells into Tscm. This novel approach establishes significantly effective tool for the generation of high-fidelity therapeutic T cells that are robust and patient specific. Furthermore, this proposal induces pluripotency, granting T-cells the ability to differentiate into different CD4 subtypes that can be utilized in a wide range of pathological conditions.

APPLICATION

• Enhance the therapeutic efficacy of CD4 T cells
• Ex Vivo generation of lineage specific Tscm CD4 T-cells that would give rise to specific CD4 T effector cells with specific therapeutic applications in specific diseases
• In vivo utilization of MEK-inhibitors to enhance the metabolic fitness of the CD4 T-cells
• In vivo utilization of MEK-inhibtors to enhance the therapeutic efficacy of immune-modulatory antibodies including but not limited to anti-PD1, anti-PDL1, anti-OX40, anti-GITR. 

ADVANTAGES

• Personalized therapy i.e., meeting the challenges of a particular patient’s conditions
• Generation of pluripotent stem cells provides the ability to create different types of CD4 T cells that can be utilized in different pathological conditions
• Cells have memory functions, making them specific to a particular antigen and can give rise to highly specific and robust antigen specific effector cells
• Solves longstanding problem of T-cell exhaustion and apoptosis, brought on by infusions of T-cell derivatized in-vitro

STAGE OF DEVELOPMENT

Have generated Tscm CD4 cells and tested their anti-tumor potential in pre-clinical models. The methods for the generation of these cells and their application have been validated.

PATENTS STATUS

Patent application has been filed.

INVENTORS

Samir Khleif
Vivek Verma