Dr. Iacovos Michael, a postdoctoral fellow at the Lunenfeld who works in the lab of Dr. Andras Nagy, is exploring new ways to develop novel, protein-based drugs (called biologics) for the treatment of cancer and eye-related diseases.
In contrast to the traditional chemical-based drugs, biologics can be produced in mammalian cells. Therefore, biologics can be bioengineered using recombinant DNA technologies to alter their characteristics, such as specificity and pharmacokinetics. A prime example of biologics are monoclonal antibodies, which have revolutionized the pharmaceutical industry and are currently used for the treatment of many diseases such as cancer and autoimmune disorders.
Two of the main challenges surrounding the use of existing biologics are the lack of target specificity and their ability to target only one disease-related factor. The former can lead to side effects, and due to the latter, more than one biologic is often required to treat complex diseases such as cancer.
Dr. Michael, utilizing his Bachelor’s in pharmacy and Master’s in biochemistry, has focused his doctoral research on circumventing the challenges of current biologics by developing novel bispecific biologics that either target a disease pathway only at the desired site (e.g., the tumour microenvironment) or target two different disease-related pathways.
“Iacovos is exceptional, and one of the most talented students I’ve ever had during my career,” says Dr. Nagy. “His high level of devotion to utilize his broad range of knowledge is combined with extremely innovative thinking and approaches.”
Dr. Nagy’s lab has been studying the role of angiogenesis – the formation of new blood vessels – in normal physiology and in specific illnesses. Angiogenesis has been shown to play an important role during cancer progression, as well as in eye-related diseases such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). The main factor controlling angiogenesis is Vascular Endothelial Growth Factor-A (VEGF-A). Previous studies have shown that inhibition of VEGF-A, using anti-VEGF biologics such as antibodies (e.g. AvastinTM), delays cancer progression and improves the vision of patients with AMD and DR.
Dr. Michael developed two new classes of antiangiogenic, anti-VEGF biologics with unique advantages over the traditional anti-VEGF biologics. The first class, VEGF sticky-traps, captures VEGF and inhibits angiogenesis only at the target site, i.e., the tumour microenvironment or the eye. The second class, VEGF lassos, simultaneously inhibit two important pathways of cancer progression—angiogenesis and cancer cell proliferation.
“This new technology holds great promise for more targeted therapies, and in the near future could be further developed for the local or simultaneous inhibition of other pathways in cancer or other diseases,” says Dr. Michael. “We hope that this technology, and through our collaborations with other Lunenfeld scientists, will lead to the development of novel drugs that are more tolerable and effective for patients with cancer, as well as eye-related diseases.”
Furthermore, Dr. Michael, during his postdoctoral fellowship at the Lunenfeld, developed a novel method that allows for high-throughput, large-scale production of biologics in mammalian cells. He is currently developing the first tissue culture facility at the Lunenfeld with the aim to produce higher quantities of biologics than previously possible. Dr. Michael anticipates that this facility will help other Lunenfeld researchers to produce their protein of interest more efficiently, thus facilitating their research.
“Iacovos is able to effectively communicate his research to other scientists and to lay audiences,” noted Dr. Jim Woodgett, Director of Research at the Lunenfeld. “This is a really important skill we often overlook and played a major role in his successful bid to become the Venture Sinai Fellow last year.”
Dr. Michael has presented his work at numerous international and national conferences, such as the American Association for Cancer Research, the Gordon conference and the Keystone symposium. During his doctoral studies, he received several prestigious awards such as the Ontario Graduate Scholarship, and he was selected as the Venture Sinai Fellow for the year 2010-2011.
Dr. Michael will continue his postdoctoral training with Dr. Nagy until the end of 2012, and then he will move to Switzerland, where he will continue his research in the lab of Dr. Douglas Hanahan.