Yissum - Research Development Company of the Hebrew University

Ceramide-based Liposomal Drug for the Treatment of Multi-Drug Resistant Cancer

Posted by Yissum - Research Development Company of the Hebrew UniversityResponsive · Innovative Products and Technologies · Israel

Summary of the technology

Cluster8

nano-liposomal preparation that includes C16-ceramide, in cancer
Project ID : 12-2017-4482

Description of the technology

Category

Life Sciences and Bio Technology

Keywords

Chemotherapy, Drug resistance

* The project is conducted in collaboration withMemorial Sloan-Kettering Cancer Center.

Application

Cells with multidrug resistance (MDR) due to aberrant expression of the lipid transporter P-glycoprotein (P-gp) display a wide range of biochemical changes that affect membrane lipid composition. Despite significant clinical effort, no effective therapy currently exists to reverse P-gp mediated MDR in human cancers.

Our Innovation

The inclusion of C16:0 ceramide, but no other natural ceramide species, in a nano-liposomal preparation enables rapid translocation of daunorubicin from cytoplasmic vesicles to the nucleus of ADX MDR cells.

Prof. Barenholz, has previously engineered Doxil which is the first successful liposomal drug that delivers doxorubicin systemically to tumors. This project sets the groundwork for the development of C16-ceramide Doxil-like liposomes for cancer therapy through three specific in vitro and in vivo aims. Successful completion of these studies will result in a direct path of drug development.

Research Outlook

We posit that MDR chemoresistance results in part from failure to generate the fusogenic lipid ceramide in a vesicular trafficking system that normally transports daunorubicin into the nucleus, reversible by exogenous ceramide. Natural ceramides are categorized into long chain (C16:0-C20:0) and very long chain (C22:0-C24:1) species relative to the length of the N-acylated fatty acid at the second position of the sphingosine backbone.

We recently showed that different ceramide species possess distinct biologic attributes with long chain C16:0 ceramide being pro-apoptotic, while very long chain C24:0, C24:1 ceramides are anti-apoptotic. We now show that inclusion of C16:0 ceramide, but no other natural ceramide species, in a nano-liposomal preparation permits rapid translocation of daunorubicin from cytoplasmic vesicles to the nucleus of ADX MDR cells.

Opportunity

The study identifies a new facet of the P-gp multidrug resistance phenotype involving disordered sphingolipid metabolism resulting in defective vesicular trafficking of chemotherapeutic drugs to the nucleus, a prerequisite for drug-induced cell killing. Altered sphingolipid metabolism can be corrected by provision of specific ceramide species resulting in correction of the trafficking defect and markedly enhanced tumor cell death. The study serves as the basis for development of a nano-liposomal ceramide chemotherapeutic delivery system for specific correction of P-gp-driven multidrug resistance in cancer.

Project manager

Shani Bullock
VP, Business Development, Healthcare

Project researchers

Yechezkel Barenholz
HUJI, School of Medicine - IMRIC
Biochemistry and Molecular Biology

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About Yissum - Research Development Company of the Hebrew University

Technology Transfer Office from Israel

Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. Founded in 1964 to protect and commercialize the Hebrew University’s intellectual property. Ranked among the top technology transfer companies, Yissum has registered over 8,900 patents covering 2,500 inventions; has licensed out 800 technologies and has spun-off 90 companies. Products that are based on Hebrew University technologies and were commercialized by Yissum generate today over $2 Billion in annual sales.

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