Targeting Endothelium for Tissue-Specific Delivery of Therapeutic Agents (BIDMC 181)

Category:    Drug Delivery

KeyWords:  Epithelial;  

BIDMC ID:    181

Abstract:

Caveolae of endothelial tissues are involved in the transport of extracellular material into and across the endothelium (to targeted tissues). These invaginations in the cell plasma membrane pinch off and traverse the cell without entering the lysosomal degradation system. The inventors have developed techniques to identify, isolate and purify caveolae microdomains from a wide variety of tissues. Moreover, they have produced monoclonal antibodies specific for these microdomains and proteins therein. The in vivo data support claims of selective uptake of radiolabeled MAb’s to tissues by targeting their caveolae and microdomains therein. Additionally, they claim caveolae specificity between the vascular beds in differing organs (liver, lung, brain, kidney, etc.). Within these organs, it appears that the caveolae of tumor endothelium are sufficiently different from normal tissue endothelium to allow selective targeting of these malignant structures.

Inventor:   Jan Schnitzer, MD, presently Scientific Director, Professor Director of Vascular Biology and Angiogenesis Program, Sidney Kimmel Cancer Center

Commercial Opportunity:

The potential market is extremely wide. By use of a targeting agent such as a monoclonal antibody attached to a drug, exquisite selectivity and uptake could potentially be achieved. This additional selectivity would be applicable to existing drugs currently used systemically now (likely parenteral administration). The inventor has proof of concept in the isolation methods of caveolae and their constituents. Additional proof of concept include the development of MAb’s to these microdomains and proteins within the caveolae, and the successful targeting of radiolabeled MAb’s to tissue specific caveolae (and transport to underlying tissue) in vivo. Additional work demonstrates selectivity between tumor caveolae and normal tissue caveolae.

Competitive Advantages:

Related Publications:

PNAS (2002) Feb 19: 99(4):1996-01. Targeting endothelium and its dynamic
caveolae for tissue-specific transcytosis in-vivo: a pathway to overcome cell
barriers to drug and gene delivery

State of Development:

Related Technology URL:

Patent Status:

3 issued US, CIP pending, 1 PCT pending:
Isolation and uses of caveolae, US 5,776,770 and US 5,914,127
Tissue-Specific Monoclonal Antibodies, US 6,255,457 B1
Isolation of Microdomains of Caveolae and GPI-Anchored Proteins, PCT/US96/14177

TVO Contact Info:
     Catherine M Lenich
     Senior Associate TVO
     clenich@bidmc.harvard.edu
     Phone: 617-667-0568   Fax: 617-667-0646

     Beth Israel Deaconess Medical Center
     Technology Ventures Office  Room: BR-0200
     330 Brookline Avenue
     Boston, MA 02215