Medical Student Research Fellowship for Summer 2007

Mentor: Philip Thorpe / Xianming Huang
Department: Pharmacology
Room number: NC7.304
Mail Code: 9041
Phone number: 81268 / 81623
E-mail: philip.thorpe@utsouthwestern.edu / xianming.huang@utsouthwestern.edu
Project title: In vitro characterization of a new anti-PS antibody

Human subjects IRB approved project number (where applicable): NA

Animal subjects IRB approved project number (where applicable): NA

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)

Basic Research

Brief Description of Project:

It has been demonstrated that phosphatidylserine (PS) is a specific marker for tumor blood vessels. To target PS on tumor vasculature, we have raised monoclonal antibodies that recognize PS and have shown that they localize specifically to tumor blood vessels following injection into tumor bearing mice. Treatment of tumor bearing mice with one of the antibodies, 3G4, results in 50-90% tumor growth retardation. 3G4 enhances the antitumor effects of common radio-and chemo-therapeutic strategies. In vitro and in vivo studies indicate that 3G4 acts by provoking innate autoimmune reactions that destroy tumor blood vessels. In addition, the antibody appears to negate PS-mediated immunosuppressive signals generated by the vascular endothelium and received by monocytes/macrophages. A mouse-human chimeric version of 3G4, called bavituximab, is currently in Phase I and II clinical trials in patients with various solid cancers.

A new, wholly human anti-PS antibody has recently been generated. The new antibody is potentially superior to bavituximab for human clinical trials because it is less likely to evoke immune responses to the antibody in humans. This project will focus on characterization of the new antibody in vitro, including binding profiles and functional assays, such as the cell proliferation assay.

Previous Research Activities or Publications with Medical Students: