FHS seminar series by Dr. Dimiter Dimitrov

Dr. Dimitrov joined the National Cancer Institute (NCI) of the National Institutes of Health (NIH), USA, in 1990. He was tenured as Senior Investigator in 1993 and appointed at the Senior Biomedical Research Service in 2008. His research group includes molecular biologists who are experts in display/screening/libraries methodologies, antibody engineering, and protein biochemistry. His major long-term goal is the development of clinically useful therapeutics and vaccines based on human monoclonal antibodies including engineered antibody domains. He has authored and coauthored more than 390 articles cited more than 20,000 times, and is inventor or co-inventor of more than 90 inventions, patent applications or patents.

I will discuss our group work on the identification, characterization and engineering of human monoclonal antibodies (mAbs) in IgG1, Fab, scFv, VH and CH2 formats, and as antibody drug conjugates, chimeric antigen receptors (CARs) and bispecific antibodies. Two of the candidate therapeutic mAbs against cancer are now in clinical trials as CARs and I will emphasize the role of the epitope for the success of one of them (against CD22). Our most important engineered antibody and CD4 domains are those against HIV-1 with the goal of HIV-1 eradication – will present recent unpublished data from animal studies demonstrating the exceptional potency of our bispecific multivalent fusion protein based on one-domain soluble CD4 and the antibody domain m36.4 targeting coreceptor binding site. I will also discuss our full-size mAbs against emerging and biodefense-related viruses with an emphasis on henipaviruses and coronaviruses mostly MERS-CoV especially for prophylaxis and therapy of humans. One of these antibodies, m102.4, is approved for use in humans exposed to Hendra virus on a compassionate basis in Australia.