Synergistic Antitumor Activity of Combination Immunotherapy IL-4 receptor targeted agents and Interferons -alpha and -gamma
In 2019, an estimated 22,530 women will receive a new diagnosis of ovarian cancer and an estimated 13,980 women will die from the disease. Ovarian cancer is the fifth most common cause of cancer death in the United States for women. The prognosis, if detected early, has a relative survival rate of ~92% with treatment. However, only about 14.8% of ovarian cancers are detected in its early stages. The majority (80%) of ovarian cancers are diagnosed at the advanced (stage III and IV) stages of the disease, which is associated with poor long-term survival rates. Due to the lack of an effective screening test or treatment options of advance stage ovarian cancer, there is a need for newer, more effective treatments for ovarian cancers.
FDA Researchers developed a combination treatment of a recombinant chimeric protein comprising of an anti-interleukin-4 (IL-4) conjugated to a Pseudomonas exotoxin (IL-4-PE38KDEL), interferon alpha (IFNα) and interferon beta (IFNγ). The combination of IL4-PE and IFNs targets cancers that express IL-4R, such as in ovarian cancers. In in vitro studies with human ovarian, epithelial carcinoma cells, the combination therapy demonstrated a synergetic cytotoxic effect against the cancer cells tested. In in vivo human, ovarian mouse model studies, the IL4-PE and IFNs combination increased the overall survival of tumor-bearing mice by targeting the proliferation of tumor cells without causing histological damage to vital organs.
Potential Commercial Applications
- Targeted treatment to delay progression and to maintain the patient’s quality of life with the intent of achieving complete remission or a cure
- A combination therapy that synergistically targets cancers that express IL-R, such as ovarian cancers
Development Stage: in vivo, ovarian mouse model studies
Inventors: Raj Puri, Syed Husain, Daniel Green
“Combination immunotherapy with IL-4 Pseudomonas exotoxin and IFN-α and IFN-g mediate antitumor effects in vitro and in a mouse model of human ovarian cancer.” Immunotherapy 2019 Apr; 11(6): 483-496.
PCT: PCT/US2018/049919 filed 09.07.2018
Product Area: Oncology, Drugs
FDA Reference No: E-2017-025