Morphotek enters collaboration to investigate CA125 tumour antigen

Morphotek has entered into a collaborative research agreement with University of Wisconsin-Madison (UW-Madison) to investigate the immunosuppressive effects of the CA125 tumour antigen on farletuzumab.

Previous work showed that the human CA125 tumour antigen may potentially suppress immune-mediated killing of macrophages and natural killer (NK) cells by suppressing their antibody-dependent cellular cytotoxicity (ADCC) function. ADCC is an immune-mediated cell-killing process inherent to macrophages and NK cells that is activated through the engagement of monoclonal antibodies (mAbs) bound to cell-surface tumour antigens. Farletuzumab is an investigational mAb that targets tumour cells through binding the cell surface-expressed folate receptor alpha (FRA) and mediates tumour cell killing in part by ADCC. CA125 is a secreted protein highly over-expressed by the majority of ovarian cancers. Previous independent studies suggest that one of CA125’s pro-tumour functions is to enable tumours to avoid immune-mediated killing by the patient’s own immune system.

Research could potentially aid patients with malignancies over-expressing CA125

The collaboration will initially investigate the immune status of primary macrophage and NK cells derived from the blood of ovarian cancer patients with varying levels of CA125. In addition, the collaboration will test whether the farletuzumab-mediated killing of ovarian cancer cells using patient-derived immune cells is affected by tumour-derived CA125.

“We are excited to enter this collaboration with researchers at the University of Wisconsin-Madison in this innovative field of CA125-mediated immune suppression,” stated Luigi Grasso, Ph.D., Chief Scientific Officer of Morphotek. “Our efforts to understand the mechanisms by which tumours evolve to evade immune surveillance, including ADCC suppression, will continue to enable us to develop novel therapeutic agents and innovative clinical designs to overcome these mechanisms and potentially aid patients with malignancies over-expressing CA125.”

As ADCC is an important mechanism of action of farletuzumab, higher levels of CA125 may potentially disrupt the ability of farletuzumab to elicit an ADCC response, thereby lowering its anti-FRA-mediated tumour-killing potential.