Enhancing tumor immunogenicity with Hsp90 inhibition
This technology describes novel methods of combating cancerous tumor growth by pairing Heat shock protein 90 (Hsp90) inhibitors with agents shown to enhance immunogenic activity. This technology could be used to treat carcinomas, sarcomas, lymphomas, and leukemias, and as such, it will be of interest to the pharmaceutical, biotechnology, and healthcare industries.
Researchers
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combination treatments of hsp90 inhibitors for enhancing tumor immunogenicity and methods of use thereof
United States of America | Published application
Figures
Image 1: The change in tumor mass between syngeneic (C57Bl/6) and immunocompromised (NOD-SCID) mice with transplanted murine MC38 tumors receiving continuous low dose administration of Hsp90 inhibitors or a vehicle control.
Image 2: MHC Class I surface expression by Hsp90 inhibitor concentration or with a vehicle control. Since MHC Class I cells present tumor-associated antigens, more expression of these cells means greater ability to recognize and kill tumor cells.
Technology
The technology introduces a cancer treatment that involves administering both an Hsp90 inhibitor and an immunostimulant. The Hsp90 inhibitor and the immunostimulant can either be delivered together as an admixture, separately but at the same time, or one after the other. The method of administration is flexible: infiltration, injection, and oral ingestion are a few of the options. The Hsp90 inhibitor works by blocking or reducing the activity of Hsp90, such as its folding, assembly, and activation of oncogenic proteins. The action of an effective amount of an Hsp90 inhibitor—a dosage less than that which is known to be cytotoxic and delivered daily—leaves the normal function of Hsp90 in maintaining cellular homeostasis intact but interferes with Hsp90 such that the immune presentation of the tumor antigen on the cancer cell surface is enhanced. This enhancement allows for immune effector cells to selectively attack cancer cells. The immuno-stimulating aspect of the technology promotes this response, harnessing the body’s immune system to attack the cancer.
Problem Addressed
Extensive anticancer drug development efforts have centered on Hsp90, a chaperone protein involved in stabilizing proteins necessary for tumor growth or the opposite, the proper degradation of proteins. Hsp90 has been shown to have a significant effect in promoting the growth and development of a wide range of cancer-causing proteins. Hsp90 activity can thus lead to an increased rate of tumor production and a decrease in tumor cell death. Hsp90 inhibitors have consequently become an attractive therapeutic in the field of cancer therapy. However, Hsp90 inhibitors are clinically functional at doses that can be toxic to normal human cells, rendering the treatment highly immunosuppressive. Therefore, this technology aims to use a combination of more frequent, lowered doses of Hsp90 inhibitors and immunostimulatory agents to combat tumor activity without the off-target immunosuppressive effects seen in previous Hsp90-focused therapies.
Advantages
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Reduced tumor proliferation
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Can be paired with other immunogenic therapies
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Not cytotoxic to healthy human cells, unlike previous Hsp90 inhibitors
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Applicable to a wide variety of cancer types
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