Yissum - Research Development Company of the Hebrew University

Topical Treatment of Skin Toxicities Caused by Biological Anti-Cancer Drugs

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

Summary of the technology

Cluster8
Many of the antineoplastic tyrosine kinase inhibitors are associated with prominent and sometimes dose-limiting dermatologic complications. Of severe clinical implication are the specific EGFR inhibitors. Most patients treated with these drugs suffer from severe impairment to their quality of life and require reduction or interruption in the anti-cancer drug protocols. Treatment strategies today for treating skin toxicities from EGFR inhibitors show limited benefit and most patients require dose reductions or interruptions to the anti-cancer treatment protocols.
Our proposal focuses on the development of a novel approach using formulation for treating skin toxicities caused by anti-neoplastic EGFR inhibitors by applying topical compounds that specifically and locally block the anti-cancer drugs. Our preliminary results have shown that blocking EGFR inhibitors binding to EGFR prevents keratinocyte death. We have identified small compounds that block EGFR inhibitors binding to its receptor and have developed topical slow release system that can deliver the target compounds to the hair follicle which is a major target for skin rash caused by EGFR inhibitors. Our novel approach will improve the quality of life of patients suffering from skin toxicity and help maintain an optimal anti-neoplastic dose thereby allowing more patients to receive full dose anti-cancer therapy and improve response to therapy
Project ID : 6-2017-4450

Yissum - Research Development Company of the Hebrew University
Yissum - Research Development Company of the Hebrew University
Yissum - Research Development Company of the Hebrew University

Description of the technology

Dr. Sharon Merims, Hadassah Medical Center

Category

Life Sciences and Biotechnology

Keywords

EGFR inhibitor, skin toxicity, topical

Current development stage

TRL3 - hypothesis testing and initial POC demonstrated in limited # of in-vitro models

Application

  • Many of the antineoplastic tyrosine kinase inhibitors are associated with prominent and sometimes dose-limiting dermatologic complications. Of severe clinical implication are the specific EGFR inhibitors.
  • Most patients treated with these drugs suffer from severe impairment to their quality of life and require reduction or interruption in the anti-cancer drug protocols.
  • Treatment strategies today for treating skin toxicities from EGFR inhibitors show limited benefit.

Our Innovation

A novel approach for topical slow release system treating skin toxicities caused by anti-neoplastic EGFR inhibitors and tyrosine kinase inhibitors

  • Applying topical compounds that specifically and locally block the anti-cancer drugs.
  • Cell viability improvement.
  • Delivery of drug to the hair follicle.

Pre-Clinical Results

  • Our finding uncover specific small molecules that were topically applied and delivered via a slow release system from biodegradable polymers to construct nanoparticles that penetrate the deep layers of the epidermis which are dense with EGFR.
  • Cell death inhibition induced by marketed anti-EGFR antibodies was observed.
  • The slow release system provides a long term protection to the skin tissue from the damage of the systemic administration of the biological drug.
  • The particles can accumulate in the hair follicle, locally remain in this site over time and do not penetrate through skin.


Fig. 1: C-1 improves viability of A431 cell cetuximab induced cell death by more than 50%.

Fig.2: Protective effect of C-1 and C-2 compounds on HaCaT cell line. 2uM C-1 compound improved viability of cetuximab treated HaCaT cells by 100% and 2uM C-2 compound improved viability of HaCaT cells by 62%.

Fig. 3: Biodegradable nanoparticles penetrate human skin and accumulate in the hair follicle and sebaceous glands. A) Accumulation of fluorescently labelled nanoparticles (in green) in hair follicles and sebaceous glands in close proximity to EGFR (labelled in red). B) Higher resolution of hair follicle in a depicting overlay of nanoparticles and EGFR seen in yellow.

Opportunity

  • Improve the quality of life of oncology patients suffering from skin toxicity.
  • Maintain an optimal antineoplastic dose allowing more patients to receive full dose anticancer therapy, thus improve response to therapy.

Project manager

Ariela Markel
VP, Business Development, Healthcare

Project researchers

Ofra Benny
HUJI, School of Medicine - IMRIC
School of Pharmacy- Institute for Drug Research

Sharon MERIMS
,

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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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