CHIMERIC ANTIGEN RECEPTOR-MODIFIED GRANULOCYTE-MACROPHAGE PROGENITORS FOR CANCER IMMUNOTHERAPY

Smart overview of the Invention

Methods have been developed to genetically modify granulocyte-macrophage progenitors (GMPs) to express chimeric antigen receptors (CARs). These CAR-GMPs can be expanded and cultured under defined conditions, allowing for a significant increase in their quantity while retaining their ability to differentiate into functional immune cells.

Importance of GMPs in the Immune System

Granulocytes and macrophages, derived from GMPs, are crucial components of the innate immune system. They serve as the body's first defense against infections and play a role in maintaining overall health. However, challenges in long-term expansion of GMPs have limited their therapeutic potential.

Enhanced Therapeutic Applications

The disclosed methods enable the long-term culture of GMPs, which can then be engineered to specifically target and eliminate cancer cells. These CAR-GMPs have shown efficacy in preventing bacterial infections in animal models, highlighting their potential for broader applications in immunotherapy.

Culturing Conditions for CAR-GMPs

The culture conditions for CAR-GMPs include specific growth factors and inhibitors that maintain their morphology and functionality during expansion. Key components involve a combination of defined culture media, such as DMEM/F12 mixed with Neural Basal Medium, along with various supplements to support optimal growth.

Differentiation into Immune Cells

After expansion, CAR-GMPs can be induced to differentiate into various immune cells, including macrophages and granulocytes. This differentiation is achieved using specific colony-stimulating factors that facilitate the expression of CAR, thereby enhancing the ability of these cells to target tumors effectively.