In this interview, Andreas Plückthun reviews the landscape of challenging antibody targets—membrane proteins, intracellular proteins, and glycans—and surveys the diverse strategies being employed to tackle them, ranging from conventional lead optimization to high‑throughput panning, advanced screening, and fully computational antibody design (with experimental verification only). He highlights that while engineering technologies have steadily improved across the board, the biggest bottleneck remains a limited biological understanding of disease mechanisms and how they connect to specific molecular targets. Plückthun also emphasizes the importance of scientific conferences as hubs for direct interaction, networking, and idea exchange among academia, biotech, and pharma, noting that the blend of “crazy” academic ideas with industry perspectives fuels ongoing innovation in the antibody field.
Chapters
Yeah, this session was about difficult targets, and we heard quite a variety of different approaches to these targets. The first half was about membrane proteins, and we heard about very different approaches to them by optimizing the targets, by taking some leads malignant by taking very conventional approaches and then go through several rounds of engineering or throwing everything at difficult targets, as well as the difficulty of getting binding proteins to intracellular targets, to finally glycans, and to finally come up with antibodies by computer design exclusively without doing any experiments. Only in verification. So I think it's a very exciting overview of different approaches, different technologies going at very, very difficult questions. Actually, a lot of progress has been made in antibody engineering. We have seen advances at all levels, from panning technologies, computer design, better approaches from screening. So there's a lot of gradual improvements at all levels that really makes this a very robust technology. What really is lacking is biological understanding, and this has been a much more difficult question than people believe, and this has to do with a lack of understanding of some of the key features that drive a disease and connect this to a particular molecule. And it is actually there that I think the war will be won or lost in making this connection to biology. And I think we all have to admit that our understanding is much, much less than we would like. Well, I think a very important part of going into a conference at all is to meet colleagues and to chat with them. Catch up what's been going on. And this is of course one of the reasons coming to this place in the first place is not only to listen to the talks, some of the information you could also get from reading papers, but really the direct interaction I think is very important. And to see what's going on from the exhibitors and also from the posters is of course a very additional and important additional bonus that you get going to the exhibition hall. Well, I think it's still one of the conferences in this space, and of course there are many now, many alternative conferences addressing the same space, but this has by now achieved a tradition and core people come and meet and exchange ideas. And also I think what's very important is the percentage of academics bringing in some crazy ideas which may only pan out much, much later keeps this, I think, a very lively conference. I think this very good mixture between pharma industry, biotech, and academic is what makes this a very unique mixture. It's very international and has been a very changing program. It's not always the same, and therefore it's a very exciting place to come to all the time.
