Dual Specific Anti-CD22 Anti-CD19 Bicistronic Chimeric Antigen Receptors (CARs)

Treatment of B-cell acute lymphoblastic leukemia (ALL) and lymphoma using chimeric antigen receptors (CARs) targeting B-cell surface protein CD19 has demonstrated impressive clinical results in children and young adults. Despite the promising results from CD19 CAR therapy, up to 40% of patients, who initially achieve remission, eventually relapse. Relapse or non-response to CD19-directed CAR therapy may be due to low or diminished CD19 expression. Such patients would be predicted to benefit from CAR therapies targeting other B-cell surface proteins, such as CD22.

Scientists at the National Cancer Institute’s (NCI) Pediatric Oncology Branch have developed a novel, bicistronic CAR construct targeting both CD19 and CD22 simultaneously. Specifically, the construct encodes both CD19 and CD22 on the same vector, ensuring comparable levels of targeting activity against both proteins. CAR-T cells produced with this construct eradicated relapsed ALL models, including one derived from a patient that displayed relapse after CD19-directed therapy. To date, this bicistronic approach exhibits the best results in CAR-T models of pre-B cell ALL.

NCI is actively seeking parties interested in licensing this invention to commercialize the bicistronic CAR construct targeting CD19 and CD22 for immunotherapy.