Melbourne company Cartherics is joining forces with the Zucker Institute at the Medical University of South Carolina to investigate whether a novel antibody can strengthen next-generation immune cell therapies for solid tumours and endometriosis.
The collaboration will combine Cartherics’ induced pluripotent stem cell-derived natural killer cell platform with an antibody that targets tissue factor, a protein implicated in tumour growth, blood vessel formation, invasion and metastasis. The antibody was developed by Associate Professor John Wrangle at MUSC and Dr Alessandra Metelli of Italy’s Regina Elena National Cancer Institute.
Under the research collaboration and option agreement, the partners will assess whether the antibody can be incorporated into CAR NK cell therapies designed to attack tissue factor-expressing cells. Initial work will explore potential applications in cancers including ovarian cancer and triple negative breast cancer, as well as in endometriosis.
Tissue factor has emerged as a target of increasing interest in oncology. It is expressed in a wide range of solid tumours and is involved in biological processes that can help cancers grow, spread and resist treatment. The US Food and Drug Administration has already clinically validated the target by approving tisotumab vedotin, an antibody-drug conjugate for recurrent or metastatic cervical cancer.
Interest in tissue factor is also growing beyond cancer. Abnormal expression has been identified in endometriosis, a chronic condition in which tissue resembling the lining of the uterus grows outside the uterus and can cause severe pain, infertility and other complications. Cartherics believes this may open a new therapeutic avenue in a disease that has historically had few targeted treatment options.
The MUSC and Regina Elena researchers say their antibody was designed to be highly specific, aiming to improve safety relative to other tissue factor-targeting antibodies. The collaboration will test its performance in laboratory and animal models of cancer and endometriosis.
Professor Wrangle said tissue factor remained an important but underexplored therapeutic target.
“We now know that tissue factor is not only present on a huge number of cancers, including ovarian cancer, but also is integral to how cancers grow, survive and resist our best therapies,” he said. “The purpose of Dr Metelli’s and my science is to learn how to safely kill cancer cells that sustain themselves with tissue factor.”
Cartherics chief scientific officer Dr Walid Azar said the agreement created an opportunity to apply the company’s established induced pluripotent stem cell-derived CAR NK platform to a new target.
“We are delighted to incorporate this innovative antibody technology into Cartherics’ established iPSC-derived CAR NK cell platform,” Dr Azar said. “We believe this collaboration provides an exciting opportunity to develop next-generation cell therapies for patients with limited treatment options.”
Cartherics is developing off-the-shelf immune cell therapies, with a particular focus on women’s diseases including ovarian cancer and endometriosis. Its platform uses induced pluripotent stem cells generated from donated cord blood, which can be engineered and differentiated into natural killer cells, T cells and other immune cells.
Unlike personalised cell therapies made individually for each patient, an off-the-shelf approach aims to create a banked treatment that can be manufactured at scale and supplied when needed. The company’s lead candidate, CTH 401, is a CAR-induced natural killer cell product directed at TAG 72, a tumour-associated target. It is being developed for ovarian cancer and other solid tumours.
The latest partnership adds tissue factor to Cartherics’ development agenda and reflects the wider effort to make cell therapies work more effectively in solid tumours. While engineered cell treatments have transformed care for some blood cancers, solid tumours present tougher biological and manufacturing challenges, including heterogeneous targets, an immunosuppressive tumour environment, and barriers that can prevent immune cells from reaching cancer cells.
