Targeted cargo protein combination therapy
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Publication Number
US-9629899-B2
Publication Date
2017-04-25
Expiration Date
2029-10-14
Abstract
The present invention combines a targeted cargo protein with an active agent for the treatment of a disease or condition.
Core Innovation
The invention combines a targeted cargo protein with an active agent for treating diseases or conditions characterized by cells expressing specific cell surface molecules, such as cancer cells. The targeted cargo proteins comprise a targeting moiety linked to a cargo moiety that kills or inhibits the growth or function of the target cells. This combination therapy is intended to synergistically enhance treatment effectiveness, exemplified by the combination of an IL-4 receptor-targeted cytotoxin (PRX321) with gemcitabine for pancreatic ductal adenocarcinoma (PDA).
The invention is based on the discovery that targeted cargo proteins such as PRX321, when combined with chemotherapeutic agents like gemcitabine, have a synergistic antitumor effect both in vitro and in clinically relevant animal models. This results in significant tumor burden reduction and improved survival compared to either agent alone. The invention provides compositions and methods involving these targeted cargo proteins in combination with active agents that employ independent mechanisms of action, thereby enhancing cancer therapy specificity and effectiveness while limiting toxicity to normal tissues.
Claims Coverage
The patent includes one independent claim detailing a method of inhibiting cancer cells overexpressing IL-4 receptor using a combination therapy.
Targeted cargo protein PRX321 binding specifically to IL-4 receptor
The method involves contacting cancer cells with a targeted cargo protein PRX321 that has a targeting moiety that specifically binds to IL-4 receptor and a cargo moiety that inhibits the cancer cell.
Combination with an active anti-cancer agent
The method further involves contacting the cancer cell with an active anti-cancer agent which is known to provide therapeutic benefit in combination with the targeted cargo protein.
The claims cover a method of treating cancers overexpressing IL-4 receptor by combining a targeted cargo protein PRX321 with various active anticancer agents, including chemotherapeutic agents and antibodies, to achieve synergistic inhibition of cancer cell growth.
Stated Advantages
Synergistic enhancement of anti-tumor effects when targeted cargo protein PRX321 is combined with chemotherapeutic agents such as gemcitabine.
Improved survival and tumor burden reduction in pancreatic cancer models compared to treatment with either agent alone.
Enhanced specificity and direct toxicity toward tumor cells overexpressing the IL-4 receptor, limiting toxicity to normal tissues.
Potential for lower therapeutic doses due to synergy, possibly reducing side effects.
Documented Applications
Treatment of pancreatic ductal adenocarcinoma (PDA) using combination of PRX321 and gemcitabine.
Treatment of cancers overexpressing IL-4 receptors, including brain cancer, Kaposi sarcoma, bladder cancer, renal cell cancer, breast cancer, non-small cell lung cancer, thyroid cancer, squamous cell carcinoma of head and neck, colon cancer, gastrointestinal cancers, mesothelioma, prostate cancer, and hematological malignancies.
Use in inhibiting growth of tumor cells overexpressing IL-4 receptor.
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