This is aimed at the pre-clinical development of soluble EphB4-HSA (sEphB4-HSA) and its ultimate commercialization for the treatment of various cancer types. sEphB4-HSA was chosen as a pre-clinical due to better efficacy in direct comparisons in xenograft models. Studies with the sEphB4-HSA fusion protein dosed every 3 days display potent anti-tumor effects in multiple xenograft studies. We have generated a mammalian cell line that expresses high levels sEphB4-HSA and have developed a scaleable purification protocol for sEphB4-HSA for in depth pharmacokinetic analysis and xenograft studies. Specifically, dose escalation studies will be performed to identify any non-linearities in the pharmacokinetics of the fusion protein and as guidance in dosing Xenograft models. Xenograft studies will be performed in addition to those already performed to determine if there are particular tumor types that are more susceptible to sEphB4-HSA treatment than others by direct comparison with AvastinTM. Additionally, immunogenicity will be monitored in immunocompetent rodents using sEphB4-HSA and mouse specific fusion protein (msEphB4-MSA) and preliminary toxicology screens will be performed.

Public Health Relevance

Soluble EphB4-HSA inhibits the interaction between EphB4 receptor kinase and its cognate ligand EphrinB2 and bidirectional signaling. EphB4-EphrinB2 are expressed on venous and arterial endothelium and critically required for maturation of newly forming vessels. sEphB4 inhibits angiogenesis in response to various vascular growth promoting agents and thus has a broad and novel anti-angiogenic activity. EphB4 is also highly induced in many cancers and sEphB4 has direct tumor cell cytotoxicity. sEphB4-HSA thus may impact survival and quality of life of many cancer victims.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43CA168158-01
Application #
8314951
Study Section
Special Emphasis Panel (ZRG1-OTC-T (10))
Program Officer
Zhao, Ming
Project Start
2012-09-24
Project End
2013-02-28
Budget Start
2012-09-24
Budget End
2013-02-28
Support Year
1
Fiscal Year
2012
Total Cost
$149,607
Indirect Cost
Name
Vasgene Therapeutics, Inc
Department
Type
DUNS #
018441588
City
Los Angeles
State
CA
Country
United States
Zip Code
90033
Liu, Ren; Ferguson, Benjamin D; Zhou, Yue et al. (2013) EphB4 as a therapeutic target in mesothelioma. BMC Cancer 13:269