Acute myeloid leukemia (AML is caused by a DNA mutations in the stem cells of the bone marrow. It is a disease with high rates of relapse because the mutated stem cells can not always be fully eliminated. T-cells are a part of the immune system and develop from the stem cells in the bone marrow. They help protect the body from infection. Recently, treatments that redirect the T cells are being developed to help fight the growth of leukemia cells.

AML has a unique expression pattern C-type lectin-like molecule-1 (CLL-1). This molecule is found in leukemia stem cells but is absent in normal stem cells. Therapies that target this molecule can be very effective. ABL Bio announced at the annual ASH conference in December 2021 that they have developed ABL602, an immunoglobulin G(IgG)-based bispecific antibody that targets CLL-1. “According to the company, ABL602 demonstrated higher binding activity to CLL-1 expressing AML cell lines and greater tumor-killing effect.”

“Despite strong tumor-killing activity, ABL602 did not kill CLL1-negative cancer cell lines, suggesting that ABL602 induces CLL-1-dependent cytotoxicity (a substance or process that causes cell damage or death).” In established orthotopic (a body with tissues and organs in their usual place) AML models, ABL602 demonstrated statistically significant anti-tumor activity. Parts of bone marrow CD33 and AML blasts decreased in a dose-dependent manner.

Overall, ABL602 is appropriately engineered to “promote T-cell activity specifically against CLL1-expressing AML cells and is a promising treatment strategy for AML patients by achieving the desired balance between antitumor activity and safety.” At the European Society for Medical Oncology (ESMO) 2022 in September, ABL Bio will provide it’s pre-clinical trial data in one of the key oral presentations.