CT-011 is a humanized monoclonal antibody (mAb) that modulates the immune response and inhibits tumor growth and the spread of metastases. CT-011 interfers with the function of PD-1 (Programmed Death-1), an inhibitory receptor belonging to the B7-receptor family that is expressed on lymphocytes and myeloid cells. Mechanistically, CT-011 inhibits the function of PD-1, resulting in the attenuation of apoptotic processed in lymphocytes, primarily effector/memory T cells. CT-011 also augments anti-tumor activities of NK cells. The enhanced activities of T and NK cells are translated into the intensification of anti-tumor immune response and the generation of tumor-specific memory cells. CT-011 is being developed as a treatment for hematological malignancies and solid tumors.
PD-1 and its ligand, PD-L1, have been demonstrated to play a central role in tumor recurrence and progression . The presence of these molecules on different tumors including different kinds of lymphoma, colorectal carcinoma, renal cell carcinoma and others, has been associated with poor prognosis and their expression was correlated with immune suppression at tumor-involved sites.
The efficacy of CT-011 was studied in a variety of experimental tumor models for leukemia/lymphoma, melanoma, lung, colon, fibrosarcoma, breast cancer and more. In all these models, single or multiple antibody doses administered 10–14 days post tumor inoculation were able to inhibit tumor growth, to extend the survival of tumor-bearing mice, and to generate tumor-specific protection against tumor re-challenge.
A Phase I, dose escalation, clinical study in 17 hematological malignancy patients has been completed. The study showed that a single administration of CT-011 (0.2 to 6.0mg/kg) was overall safe and well tolerated with no observed serious/unexpected treatment-related adverse events and no observed infusion-related responses or autoimmune reactions. No single dose MTD could be established in this study. Interestingly, apparent clinical responses were observed in six of the patients exhibited as extended survival as follows: one Complete Remission (NHL - follicular lymphoma), four Stable Disease (HD, 2 CLL, and MM), and one minimal response (AML). Amongst immune modulating molecules, CT-011 presents a safe alternative exhibiting no signs of autoimmunity which commonly occurs in the presence of other immune-modulating antibodies.
A Phase II safety and efficacy study of CT-011 in patients with diffuse large B-cell lymphoma following autologous stem cell transplantation has been completed in the US and Israel. Other clinical studies evaluating the safety and preliminary efficacy of CT-011 in patients suffering from metastatic colorectal cancer and metastatic melanoma as well as from a variety of other metastatic cancer diseases are ongoing.