Israel's BioLineRx ($BLRX) has unveiled positive preclinical data for its experimental treatment for chronic myeloid leukemia, a progressive blood and bone marrow cancer.
The results, published in Molecular Cancer Therapeutics, found that BioLineRx's investigational therapy BL-8040 was effective on its own and in combination with imatinib at inhibiting human chronic myeloid leukemia cells in culture and on human tumors that were engrafted in mice. According to the findings, BL-8040 treatment induced programmed cell death of tumor cells in vitro and had a synergistic effect with imatinib at low doses.
When combined with low-dose imatinib in mice engrafted with chronic myeloid leukemia tumors, BL-8040 significantly inhibited tumor growth, achieving a 95% suppression. The drug also reversed the protective effect of the bone marrow stroma on leukemia cells, which induced programmed cell death.
Chronic myeloid leukemia is characterized by production of too many white blood cells, which is caused by a constantly producing active oncogenic tyrosine kinase. Tyrosine kinase inhibitors like imatinib mesylate (Gleevec) have revolutionized the treatment of chronic myeloid leukemia and are the go-to drugs for many patients. But some patients have dormant leukemic stem cells that are resistant to tyrosine kinase inhibitors, making them susceptible to leukemia resistance and recurrence and underscoring the need for new drugs to target these stem cells. In these patients, their bone marrow microenvironments protect dormant leukemic stem cells from therapy-induced cell death.
BL-8040 acts as an antagonist for CXCR4, a chemokine receptor directly involved in tumor progression, growth of new blood vessels in the tumor, metastasis and cell survival. CXCR4 is overexpressed in more than 70% of human cancers and is often associated with disease severity.
BioLineRx currently is studying the investigational drug in Phase II clinical trials for acute myeloid leukemia and hopes to begin Phase I trials for BL-8040 for stem cell mobilization in the second quarter of this year.
- see the study abstract
- read the press release