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Fully Human Antibodies and Antibody Drug Conjugates Targeting Tumor Endothelial Marker 8 (TEM8) for the Treatment of Cancer

20:00 EDT 18 Jun 2018 | NIH

The tumor microenvironment consists of a heterogenous population of cells which includes tumor cells and tumor-associated stroma cells (TASCs). The TASCs promote tumor angiogenesis, proliferation, invasion and metastasis. Because stroma cells are found in both healthy and cancerous tissue, targeting the tumor stroma has been difficult due to the lack of targets with high tumor specificity. TEM8 (also known as ANTXR1) is a cell surface tumor endothelial marker that is most highly expressed in human tumor-associated stroma of pancreatic, breast, colon, lung, esophageal, bladder, and ovarian cancers. While low levels of expression are seen in healthy kidney, lung, and brain tissue, preliminary toxicity studies suggest limited, if any, toxic effects in these tissues. This differential expression makes TEM8 an attractive potential target for ADC development due to the ability to selectively target TASCs in many different tumor types.

Researchers at the National Cancer Institute (NCI) have developed fully human monoclonal antibodies and antibody-drug conjugates (ADCs) that target TEM8. The antibodies and ADCs have been tested both in vitro and in vivo and have shown promising data. Monomethyl auristatin E (MMAE)-conjugated TEM8 ADCs led to the eradication of large established tumors and metastases and improved long-term overall survival in mouse models. In addition, the ADC was evaluated in preliminary toxicology studies where it showed limited off-target toxicity.

IC: 
NCI
NIH Ref. No.: 
E-344-2013
Advantages: 
  • Possible to simultaneously target both tumor cells and tumor stroma;
  • Potentially superior adverse events profile than existing agents due to the differential expression of TEM8 on tumor and normal stroma;
  • Fully human antibodies are less likely to be recognized and cleared by the immune system upon repeated administration;
  • Relevance to a wide range of cancers – representing several major market opportunities;
  • High cellular internalization;
  • Cross-reactive with mouse and monkey TEM8 making preclinical studies easier and more informative.
Applications: 
  • Antibody-drug conjugates (ADCs) for the treatment of cancer
  • CAR-T cell therapy
  • Diagnostic agent for detecting and monitoring TEM8-expressing malignancies.
  • A component of multi-specific antibody therapies
Development Status: 

Pre-clinical (in vivo)

Updated On: 
Jun 19, 2018
Provider Classifications: 
Date Published: 
Tuesday, June 19, 2018
Publications: 
Patent Application: 
15/680,177
Patent Authority: 
US
Patent Number: 
9,765,142
Licensing Contacts: 
Lead Inventor: 
Inventor IC: 
NCI
NCI
Inventor Lab URL: 
https://ccr.cancer.gov/Mouse-Cancer-Genetics-Program/brad-st-croix
https://ccr.cancer.gov/Cancer-and-Inflammation-Program/zhongyu-zhu
LPM FIrst Name: 
John
LPM Last Name: 
Hewes
Inv Is lead: 
LPM Phone: 
240-276-5515
LPM Suffix: 
Ph.D.
LPM Organization: 
NCI - National Cancer Institute
DTDT Classification: 
Therapeutics
DTDT Description: 
Therapeutics
Pat Filing Date: 
2016-04-08
2017-08-17
Publication Link: 
https://www.ncbi.nlm.nih.gov/pubmed/29863500
Publication Caption: 
PMID
Publication Title: 

C. Szot et al. Tumor stroma-targeted antibody-drug conjugate triggers localized anticancer drug release.

Additional Patents: 
Applications filed in Canada, Japan, Australia, China, and Mexico.
Collaboration Sought: 
Yes
Institute or Center: 
Collaboration Opportunity: 

Licensing and research collaboration

E Number Only: 
E-344-2013
Inventor First Name: 
Dimiter
Brad
Zhongyu
Enrique
Michelle
Saurabh
Gary
Dean
Inventor Last Name: 
Dimitrov
St. Croix
Zhu
Ubani
Zhan
Saha
Decrescenzo
Welsch

Original Article: Fully Human Antibodies and Antibody Drug Conjugates Targeting Tumor Endothelial Marker 8 (TEM8) for the Treatment of Cancer

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