I have been primarily interested in potential clinical applications of medical research and thus in its translational side. For my post-PhD training, we produced the first candidate drug conjugate showing anti-tumor efficacy in a hard-to-treat model of colorectal cancer, among other contributions to targeted therapy of cancer.
In my first independent laboratory, I designed and produced the first generation cytotoxin based on a wild-type interleukin 13 (IL-13). This cytotoxin went through Phase III clinical trials in patients with recurrent glioblastoma (GBM), which is the most prevalent malignant brain tumor, showing clinical efficacy. My laboratory discovered the first factor in GBM over-expressed in majority of tumors, but not normal brain – IL-13RA2 receptor. In 2004, I joined Wake Forest University School of Medicine.
I continued searching for targets for anti-cancer therapies and designed advanced forms of GBM-specific cytotoxins while developing the concept of combinatorial therapy of GBM. My lab was first to document the phenotypic tumor heterogeneity and then first tri-molecular signature of GBM: IL-13RA2, EphA2 receptor and fos-related antigen 1 (FRA-1). Our work has been a substrate for numerous translational applications, many tested in the clinic.
My extensive experience in successful discovery of targets specific to cancer, their pathophysiological role in cancer, and rational engineering of targeted recombinant proteins (including chimera and conjugated proteins, and peptides), enabled development of novel, specific and promising means of detecting and treating cancers over-expressing tumor-specific and tumor-associated antigens. I have a particular interest in loco-regional delivery of drugs to brain tumors, especially in the convection-enhanced delivery (CED), and a faithful large animal model of the disease, spontaneous brain tumors in dogs.
During the last 20 years, in collaboration with Dr. John Rossmeisl, we have been studying and treating dogs with primary brain tumors demonstrating significant responses. This and other research led us to begin targeting four tumor-associated receptors at once: IL-13RA2, EphA2, EphA3 and EphB2 receptors. A cytotoxin targeting all these receptors, termed QUAD-DM1, is being developed for a clinical trial in human patients while showing significant therapeutic responses in dogs with spontaneous brain tumors.