Zhiwei Hu, MD, PhD, of the Translational Therapeutics Program at the OSUCCC – James, and colleagues reported the first evidence that a molecule called tissue factor (TF) is highly expressed in TNBC — both on the surface of TNBC cancer cells and throughout most of the tumor mass. The molecule is also expressed in the inner layer of tumor blood vessels, which supply oxygen and nutrients to cancer cells and help them spread to distant organs.
Additionally, the researchers have shown that an injectable, second-generation TF-targeting therapeutic molecule can target TNBC cells in laboratory and preclinical animal models. The drug works by triggering the immune system to destroy cancer cells and to stop tumor growth.
The normal function of TF is to initiate blood clotting. The engineered second-generation molecule, known as L-ICON, works by targeting TF expressed specifically on the interior surface of TNBC cells, cutting off blood supply to the tumor vessels.
“Understanding how we can harness the immune system to selectively target TF to stop growth of cancer presents many opportunities,” says Hu, senior author of the study. “What is exciting about this study is that our data shows this second-generation drug is effective for treating TNBC, either with or without BRCA1 and BRCA2 mutations, and is more effective at penetrating and targeting the tumor microenvironment than the first-generation drug.”
Hu was involved in developing the first-generation drug, ICON, while at Yale University. Both drugs have two components: a targeting domain recognizing TF on the surface of the malignant cells paired with a natural antibody domain that activates an attack by the immune system against cancer cells that bind the engineered molecule.
The immune system then attacks tumor blood vessels, and the cancerous tissue dies from lack of blood supply. The first-generation agent is being tested in clinical trials for patients with ocular melanoma and macular degeneration. The team plans to translate the second-generation L-ICON molecule into an early-phase clinical trial for patients with TNBC.
Published in the journal Cancer Immunology Research.