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Current challenges in the design of antibody-drug conjugates

Published on September 26, 2018   51 min

A selection of talks on Pharmaceutical Sciences

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0:00
My name is Nathan Tumey and I'm going to be discussing with you this morning a little bit about some design challenges in the field of antibody-drug conjugates. Just before we get going with that discussion let me just introduce myself. I am a professor at Binghamton University in the School of Pharmacy and Pharmaceutical Sciences; I teach medicinal chemistry here. I've been here for about a year but prior to joining the faculty here at Binghamton, I spent the last 15 years in the pharmaceutical industry, most recently at Pfizer where I spent about seven years in the field of developing antibody-drug conjugate. So, my background is in chemistry, my PhD is in organic chemistry and so I'm going to be sharing with you my design perspective from the perspective of an organic chemist or a medicinal chemist. So, realize that as we discuss antibody-drug conjugates, it is a very broad field and I have my own expertise and interests in it and I will share with you some of the highlights of the way the field has been developing over the last few years from the perspective of a medicinal chemist.
1:05
I'm going to introduce to you some ADC technology, in general, just to get everybody up to the same speed and then we will dig into four components of the design of ADCs and in particular, discussing aspects of payload design, linker design, conjugation chemistry as well as factors to consider in the design of the antibody itself. Then, we'll look at our crystal ball and see where the field is going, what are some ways that the field is now different than it was just a few years ago and where it's headed.
1:36
When I discuss ADCs with people the way I like to begin is with this little picture and this is based on something Amazon presented a few years ago, an idea or concept for delivering packages around major cities in the US using drones. At a molecular level that's really exactly what we're doing with an antibody-drug conjugate. So, we have a delivery vehicle, which in our case is the antibody, which is kind of an autonomous drone in many senses just circulating through the body looking for a target of interest. When it arrives at that target of interest, it releases a payload and the payload is really what carries the biological punch for this drug moiety or for the entity that we're trying to deliver. So, the payload is what's going to be carrying out the interesting biology; whereas, the delivery vehicle is simply delivering the payload to the right address.

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Current challenges in the design of antibody-drug conjugates

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