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3-o-sulfo-galactosylceramide Analogs as Activators of Type II Natural Killer T (NKT) Cells to Reduce Cancer Metastasis to the Lung

Summary
The National Cancer Institute (NCI) seeks research co-development partners and/or licensees for the sulfatide analog, C24:2, that is capable of activating tumor killing type II NKT cells and reducing cancer metastasis to the lung.
NIH Reference Number
E-100-2018
Product Type
Keywords
  • Natural Killer cells, T cells, NKT cells, 3-o-sulfo-galactosylceramide Analogs, Lung Cancer, Metastasis, Sulfatide Analogs, C24:2, Immunotherapy, Berzofsky
Collaboration Opportunity
This invention is available for licensing and co-development.
Contact
Description of Technology

Lung metastases are a sign of widespread cancer with poor survival rate. Lung malignancies can originate from almost any cancer type spread via the blood stream. Most common lung metastases are from melanoma, breast cancer, bladder cancer, colon cancer, prostate cancer, neuroblastoma, and sarcoma. Living more than 5 years with lung metastases is uncommon, and surgical procedures are only effective with localized lung metastases. Lung metastasis are extremely frequent and resistant to regular treatment due to immunosuppressive regulatory sulfatide-reactive type II NKT cells. Currently, there is no effective treatment that could prevent lung metastases.  Scientists at the National Cancer Institute (NCI) have developed a drug, C24:2, that is capable of specific activation of type II natural killer T (NKT) cells resulting in significant reduction of the number of lung metastases. C24:2 is a 3-o-sulfo-galactosylceramide analog of C24.1, which is a sulfatide composed of a galactose head with a sulfate group β-linked to a ceramide moiety. C24:2, recognized only by the type II NKT hybridoma, induced IL-13 production of lung cells and significantly reduced the development of lung metastasis. The inventors not only discovered a first-in-class drug C24:2, that has never been investigated before, but demonstrated its function both in vitro using hybridoma cell line, ex vivo by in vitro stimulation of lung mononuclear cells, and in vivo reducing lung metastasis in cancer bearing mice. Further, C24:2 altered the regulatory function of sulfatide-reactive type II NKT cells and resulted in a robust anti-tumor immune response. C24:2 could be used in combination with immunotherapy checkpoint inhibitors to treat and prevent lung metastases. 

The structure and synthesis procedure of C24:2 are described in Patent Cooperation Treaty PCT/US2019/023890 which corresponds to E-100-2018 and for which Dr. Jay Berzofsky is the lead inventor. The inventors have future plans to develop C24:2 into a therapeutic agent to treat lung metastases. The NCI seeks research co-development partners and/or licensees for the sulfatide analog, C24:2, that is capable of activating tumor killing type II NKT cells and reducing cancer metastasis to the lung.

Potential Commercial Applications
  • Therapeutic for lung metastases from different types of cancers
  • Modulator for regulatory type II NKT cell
  • Combination therapy with checkpoint inhibitors to prevent metastases
Competitive Advantages
  • Targets metastases from different types of cancers
  • Addresses a significant, unmet medical need given no current effective treatments for lung metastases
  • First-in-class drug with unique mechanism of action
  • Can be combined with marketed/approved checkpoint inhibitors to potentially increase treatment benefit
Development Stage
Patent Status
  • U.S. Provisional: U.S. Provisional Patent Application Number 62/648,167, Filed 26 Mar 2018
  • PCT: PCT Application Number PCT/US2019/238890 , Filed 25 Mar 2019
Therapeutic Area
Updated
Wednesday, February 24, 2021