Application

Anti-human Galectin-9-directed chimeric antigen receptor (CAR) T-cells for treatment of hematological malignancies (B-ALL, T-ALL, and DLBCL) in normal, overweight, and obese patients.

Key Benefits

• Can be used as a stand-alone or in-combination product to treat patients with hematological malignancies, particularly overweight and obese patients.

Market Summary

Pediatric acute lymphoblastic leukemia (ALL) is a type of cancer in which the bone marrow makes too many immature white blood cells, and diffuse large B-cell lymphoma (DLBCL) occurs from the accumulation of B-cells (normal or malignant) in lymph nodes. ALL is the most common cancer diagnosed in children. Treatment for ALL and DLBCL typically involves chemotherapy given for 2 to 3 years; other treatments such as surgery and radiation therapy may be used in special circumstances. Obesity is associated with poorer event-free survival (EFS) in pediatric ALL and DLBCL. Obesity at diagnosis independently predicts likelihood of relapse and cure in preteenager and adolescent ALL and DLBCL patients. There is currently an unmet need for new therapies to (a) overcome the chemoresistance in overweight and obese patients with ALL and DLBCL, and (b) effectively treat hematological malignancies in overweight and obese patients.

Technical Summary

Galectin-9 (Gal-9) is a member of the galectin family and is a ligand for multiple receptors including Tim-3, CD44, CLEC7a (Dectin-1), and CD137 (4-1BB) which are receptors expressed primarily on immune cells. In the present invention, Galectin-9 was found to be overexpressed on ALL and DLBCL cells, with increased surface expression on malignant cells being observed when cells are exposed to adipose-rich microenvironments. Importantly, anti-Galectin-9 antibody treatment effectively kills B-cell ALL (B-ALL), T-cell ALL (T-ALL), and DLBCL in vitro and in obese mice where anticancer drugs like methotrexate, daunorubicin, doxorubicin, and vincristine are ineffective. Given these observations and the ability of anti-Galectin-9 antibody treatment to significantly extend the survival of obese mice with B-ALL, T-ALL, and DLBCL, Emory University and Children’s Healthcare of Atlanta researchers have developed Galectin-9 directed CAR T-cells using natural ligand based sc-Fvs (5 CAR constructs).

Developmental Stage

Anti-Galectin-9 CAR T-cells (5 constructs) were tested in vivo & in vitro.