Pre-BCR Antibodies for Leukemia

Pascal is developing antibodies against the pre-B cell receptor (pre-BCR) for B cell precursor acute lymphoblastic leukemia (BCP-ALL).  The pre-BCR comprises a heavy chain paired with a surrogate light chain. The two components of the surrogate light chain, VpreB and lambda 5, are expressed only on the leukemia cells and on pre-B cells, which represent a very early stage of B cell development.  Therefore, targeting these molecules will specifically eliminate the tumor cells while sparing mature, activated and memory B cells that are essential for combating infection. Pascal’s pre-BCR antibody drug candidate can kill tumor cells in cell culture and exhibits properties amenable to engineering for enhanced cancer cell destruction.

About B-cell precursor acute lymphoblastic leukemia (BCP-ALL)

BCP-ALL (also called ALL or acute lymphocytic leukemia) is the most common childhood cancer. This disease affects certain cells in the immune system, called B cells, and is caused by mutations that arise during the early development of B lymphocytes.  There remains a strong need for improved drugs to treat BCP-ALL.  Chemotherapy can induce long term remission in up to 85% of patients; however, it is very toxic, especially in children.  Treated children are typically beset with impaired growth, learning disabilities, and risk of tumors secondary to chemotherapy later in life. Patients that do not respond to first-line chemotherapy are treated with CD19 or CD22 targeting therapies such as antibodies or chimeric antigen receptor T cells (CAR-T).  These strategies can be remarkably effective, but they eliminate the ability of the patient’s immune system to generate antibodies to protect them from infection.  In addition, CAR-T treatments are difficult for patients to tolerate, with more than half requiring admittance to the intensive care unit.  In contrast, Pascal’s pre-BCR antibodies are expected to exhibit little or no toxicity while targeting just the cancer.