Antibody Therapeutics: Brigham & Women’s • Richard Blumberg
Harnessing Nature’s Defense: Antibody Breakthroughs in the War on Illness
The immune system is one of nature’s most powerful defense systems—and antibodies have become a cornerstone of modern medicine. In Episode 29, produced in partnership with Mass General Brigham for the upcoming World Medical Innovation Forum, Nic speaks with Dr. Richard Blumberg of Brigham and Women’s Hospital and Harvard Medical School. A pioneer in the field, Dr. Blumberg shares how his research path led him unexpectedly to pivotal antibody breakthroughs, the innovation process behind groundbreaking discoveries, and how antibody therapeutics have grown from a research curiosity into a force reshaping cancer, autoimmune disease, and beyond.
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Doctor Blumberg is a physician scientist who has directed a NIH funded laboratory since 1989 and an elected member of the National Academy of Medicine.
His laboratory has been historically focused on mucosal immunology with a particular emphasis on the immunological functions of the intestinal epithelium, a field that he has pioneered through the study of non classical MHC Class 1 molecules and more recently the unfolded protein response and Paneth cell function.
1:48
In addition, he's an expert in carcinoembryonic antigen cell adhesion molecule one function.
His fundamental research has significant applications to inflammation and has been highly translational, spawning several therapeutic agents that are FDA approved.
2:03
He's also an active academic leader at Brigham and Women's Hospital and Harvard Medical School, where he serves as vice chair for research for the Department of Medicine, Brigham and Women's Hospital.
Jerry S Trier, MD, Endowed Chair and Gastroenterology.
Also, BWH, previous chief of the Division of the Gastroenterology, Hepatology and Endoscopy Co, director of the Harvard Digestive Disease Center, which is funded by P3 award, and recent director of the Brigham Research Institute.
2:32
Rick, welcome to a natural selection.
Thanks, Nick.
That was a a bit of a tongue twister in reading your bio, but congratulations on such an exemplary career.
I'm really honored to have you here.
I'm honored to be with you, Nick.
Thank you.
So as a level setting question, I asked the same signature question.
2:49
Could you please let us know in simple ways what need or impact drives your work?
I'm a physician scientist and I wish there were more of us.
And having trained in medicine, I've taken an interest in certain molecular pathways and tried to find the translational juice.
3:13
I guess if you wish, that will allow them to be translated into helping people.
You know, as a, as a leader in academic medicine and letting it leading the division for 20, almost 25 years of clinicians, researchers, educators, I always had my eye always on patients.
3:32
And my division also had their eyes on patients through my leadership in the idea that we help people in many different ways.
We help people one at a time if we're a doctor in a room, but we also help people in through our research to try to figure out ways to use our knowledge to figure out tools to attack physiologic basis of disease and therefore intervene and make people better.
3:55
And so yes, what drives me is I fell in love with certain molecules as we fall in love with a little grain of sand.
And I've been trying to understand how they work and keeping my eye on the possibility that I might be able to use that knowledge to help people.
And and for those who may not know, could you give us a quick overview of what your work in antibody therapeutics is actually about?
4:17
We have historically focused on a molecule called the neonatal FC receptor.
That's been perhaps the most translational opportunity.
I I would say from the work that we've done over the years, it's a natural molecule to be thinking about biologic agents, because all biologic agents, every single one that's given to a human being works at least in part through the fact that the mediated left C receptor or FCRN protects it from degradation.
4:49
That's why antibodies have such a long half life, so that any biologic therapeutic, which is, you know, an enormous number of them now in clinical practice, all take advantage of the relationship between FCRN and the needle FC receptor.
5:05
I saw that very early.
I was very lucky and fortunate.
In July 1992, very soon after finishing my postdoc as a young assistant professor, I stumbled on evidence that FCRN might be active in adult human life.
And then that inspired me to pursue studying of this for the last 30 years, recognizing very early on that this was had great translational potential.
5:30
Being trained as a physician scientist, I always had my eyes on that obviously.
And indeed that was the case.
The neonatal LEPSI receptor not only being important for the long half life of all biologics.
That's why the Pharmaceutical industry fell in love also with that molecule also probably in in the 90s when the field started really taking off.
5:52
But it also, as we learned over the years by work for myself others that attacking this molecule, if you wish, directing antibodies themselves at the nenialectine receptor to block its protection activities for keeping the half life of antibodies in our bodies as well as the therapeutics we receive could be a means to treat autoimmune disease.
6:15
And so in terms of the therapeutics, there's two sides of the same coin.
The one side is figuring out ways to take advantage of that biology to make therapeutics better.
They have a longer half life and other properties through engineering, antibody engineering.
6:32
But the other side of the same coin is figuring out ways to block efsirin to inhibit the protection of those bad antibodies in our body that are causing autoimmune disease and therefore to treat the variety of different diseases by blocking the FCRN, not enabling it, but blocking its activity and causing the destruction of those antibodies that are causing disease.
6:52
So we went back and play with that biology in many different ways in the various things we did in our laboratory, but more in the startup companies that I was involved in to try to take advantage of both of those opportunities.
And you mentioned autoimmune disease.
7:10
What other kinds of diseases are antibody therapeutics best positioned to treat that current medicines struggle with?
Well, the the fact is, by the nature of the properties of the antigen binding site of an antibody, biologics can be used to target virtually any accessible molecule on the body.
7:31
So it's not just the treatment of autoimmune diseases.
In the treatment of autoimmune diseases, there's many different ways to use antibody therapeutics to treat the disease by blocking a number of different important molecules that are driving the autoimmune process or going directly at the jugular if you wish in the case of efserian to block the melody that controls the half life of those antibodies that are causing disease in a human for IgG mediated autoimmune diseases.
7:58
But antibodies are as you know are wonderful therapeutics.
I can't tell you how many of the drugs that were approved in 2025 by the FDA, but increasingly and I don't know the numbers, but increasingly more and more of the therapeutics that are being approved by the FDA and other agencies around the world are antibody based therapeutics as opposed to small molecules.
8:22
Because antibodies through their antigen binding site have the ability to take rather fine little details in molecules and can target precisely on a particular driver of disease and either inhibit that target, which most of them do.
8:40
Or now people are getting into the the idea of figuring out ways to agonize and make that target work even better, so-called agonistic antibodies, which is a whole new exciting area.
So the area of biologics is enormous in terms of the numbers of therapeutic antibodies that are out there to treat cancer and autoimmunity infection.
9:00
Look at the beautiful things that happened during COVID and other kinds of epidemics when we were cloning out antibodies from patients with their elite controllers, let's say, of particular diseases and finding out that secret sauce that their own evolutionary process actually created in their bodies.
9:18
And then cloning that and using as a therapeutic to neutralize passively a particular agent such as COVID or HIV or whatever.
So antibodies are just incredibly versatile molecules.
I'm delighted that I discovered the opportunity for me to get interested in this FCRN in 1992.
9:38
It was July of 92 when the post doc came into my office with a what he thought was a failed experiment, which inspired me to work on this molecule.
But since then, FCRN is woven into every biologic that's out there because you cannot understand biologic therapies if you don't understand FCRN.
9:57
So I feel very lucky that I know a thing or two about FCRN because it gives me a great opportunity to not only think about targeting other things through antibodies and their understanding FCRM biology to help to make sure those antibodies are working as best as they can, but also thinking about antibody therapeutics more generally.
10:17
So we do think about antibody therapeutics for cancer.
That's what I'm going to talk about at the WMIF, an antibody we created against the carcinoembryonic antigen cell adhesion molecule one, SECAM one.
But we spend a lot of time, most of the time at our laboratory focused on FCRN biology and both trying to understand why it does what it does and novel functions of it, novel ligands that it might engage in.
10:44
But also biologically how can we use it to target it for autoimmunity but also make therapeutics better.
So that is a a long about way of summarizing what's been inspiring me for these last three decades, but I feel very fortunate that I am working in this space.
11:05
You said something there that piqued my Spidey sense.
That you.
Stumbled across this when a postdoc had a failed experiment that led into this.
Any learnings from that experience, from taking what would presumably look like a failure into something that's such a revolutionary success?
11:23
Yeah, just being, getting a lot of training.
I, I, we, you know, I think that it's what I call, I use a Mendelian term to describe, it's called, I say use hybrid vigor to describe cross currents of training in one's career.
11:39
So one's prepared to see things, whether it's genetics in your case and other disciplines.
But it's, I was, you know, a lot of the times you're fortunate because your training LED you in a certain area and you just happened to be confronted with something that allows you to synthesize the observations.
11:59
We'll see whether AI is able to do the same thing.
I don't think it's going to be as good perhaps in terms of directing or generating or creating new knowledge because that new knowledge comes from the Pastorian event where you're prepared to see something new.
12:17
And then you recognize the opportunities for that come from those new things and see every failed experiment as a, as a, an opportunity to learn something.
I say in the early days, I used to over and over and over look at the experiments in my lab notebook just to see if there's another clue there that I missed.
12:36
That might be something that's important not to forget or to move forward with.
But it's just, it's just being lucky and being open minded and seeing failures as opportunities to learn.
And that's a wonderful example because that postdoc was very disappointed.
12:52
And if he hadn't come into my laboratory in my office rather in July 22nd, 1992, I would not be working on FCR for the next 35 years.
Yeah, I've always been inspired by Louis Pasteur saying chance favors a prepared mind, which is very similar, exactly right.
13:08
Exactly.
That's the that's that's the point, yeah.
And and your work, obviously you've been innovating on the research and clinical side, but also on the startup side.
You you Co founded Syntonics and Syntomune, which were eventually acquired by Alexion and and Biogen.
13:25
What lessons did that journey teach you about translating academic science into therapies, and how did it shape your perspective on innovation and competition in the antibody therapeutic space?
It's AI think it's a big question, Needless to say and there's many ways to answer it and I'm sure you have a lot of thoughts about it.
13:48
The first one was Syntonics in 1998.
That one I'm most proud of because that really has changed medicine a lot.
And the second one was Syntomium, which was sort of the baby brother of Syntonics.
14:03
It came out of the Syntonics business plan from 1998.
And so it has to do with my FCRN work, which I've been focused on since 1992.
So I, I think I would say Syntonics was one of the first companies that MGB started.
14:23
It was, it was started in 1998.
We started thinking about it like 9596.
There was only one person and innovation at the time, Brian Hicks.
And that company was purchased in 2007 by Biogen and then was acquired by Sanofi.
14:41
And what it did was it, it gave forth the first long acting therapeutics for haemophilia A&B.
And but not only that, but the business plan I wrote in plan I wrote in 98 was so forward thinking.
I'm so proud of it because it basically became the lightning rod for so many other things in efserian research and clinical drug development over the years.
15:04
Without going into all the details, it really jump started almost a little cottage industry that I'll be followed.
And I'm very proud of the fact that so many others then it was at the very infancy of Efserian biotherapeutics.
So I, I would syntonics and, and centimeter sort of 1 and the same.
15:24
They're equally, equally, I think important in my life for sure.
But I think they're very equally important in, in getting Efserian biology to where it is right now.
But I from my own experience, it really made me realize just how important academia, how powerful the combination could be when academia and industry with their very unique talents can get together and do great things together.
15:58
There's a lot of similarities in, in the two because they're both very scientific, Needless to say, and they're both amazing, talented people, But the process is different.
The process associated with development is very different from the process associated with fundamental discovery.
16:19
But if you can bring the two of them together and, and maybe I can give a little bit of a political note.
I wish there was more porous interactions between academia and industry.
I, I, I know there's a lot of challenges with respect to nonprofit status and so forth.
16:42
And, and that's, that's a big deal and something that needs to be protected so there's no perceived conflicts of interest.
But the more and more we can be clever about getting industry and academia to work more closely to each other, embed them in each other's essentially place of work and getting them to think together, even at the earliest stages of the discovery process.
17:07
Especially at this point of time when we as a as a, as a nation, as a, as a global population, want to use our money as effective as we can, our tax dollars as effective as we can.
To very early on to see the opportunities and get them into the clinic is a much better use of the monies from NIH and other places.
17:27
But the only thing I would say is that we're more similar than different and that we have more to learn from each other and figure out ways to to take advantage of that is what I've learned.
Because when you grow up in academia, you're all you.
You're taught.
Oh, that's industry.
17:43
This is academia.
No, that's not the way.
We're really in this together.
We have similar complementary talents and we have more to gain from each other than to be separate.
I couldn't agree with you more.
I've been on both sides of that line and I I have similar experiences in the issuance of time.
18:00
Rick, I'll, I'll jump straight to the final question, which I think is your singularly in a position to be able to answer.
So if we zoom way out, the immune system is nature's most sophisticated adaptive technology.
Do you see a future where we can harness it not only to fight disease, but also to prevent illness or even enhance human health and resilience in ways that we haven't yet imagined?
18:25
It's a yes, I, I, I think another.
Again, this is personal and this is from my own experience.
It's not necessarily with antibodies per SE, although antibodies are a part of it.
But one place that I don't think we're spending enough time.
18:43
You and I were talking about that at the very beginning when we're talking about the genetics of children, the genetics of babies to see if we can figure out genetic risk as early as possible so we can start to intervene a disease early.
One of the things I work in, in my own laboratory, which I think is very important, which intersects directly with what our discussion was, is that at the earliest days of life, our immune systems are being taught by what we see in the world.
19:13
They're taught in some to some part by in utero.
And we're with her, you know, in the, in the, in the arms of our of her moms in the uterus.
And we're receiving many kinds of signals from her moms there a lot.
There's a lot of immunologic education that's going on there, but that series of events that are occurring immediately after birth is an intense period of immune discovery for the host, for a, for a, for an early human.
19:39
And one of the things I've learned from my work and I know from my reading of the literature is that those periods of time are a very important time of imprinting.
Not in the famous duck experiment where you get imprinted and you you think that's your mother, but in terms of the imprinting that goes on in the immune system, you get a set point very early.
20:00
And I really believe that diseases start very, very early.
The very first steps in the trajectory to a disease starts in the first days of life and the first couple years of life, two to three years, which also overlaps with the time in which we're teaching and learning and generating our own unique microbiome that resides in our body that's part of self.
20:22
So I think that one really interesting way to begin to try to think and how can we gain understanding of that in a, in a means that we can intervene is to have a better understanding of that imprinting period and earliest phases of life as it occurs in relationship to the way the immune system is getting educated in the earliest days and trying to redirect and deviate the immune response to health related pathways as a route as opposed to disease associated pathways associated with autoimmunity.
20:57
I would even say the cancer predisposition may start in the earliest days of life and certainly a variety of neurodevelopmental issues start in the earliest days of life and they're immune mediated and influenced by the environment.
So I personally would like to see more resources put into that.
21:16
Well, with that, I know we're a time.
Thank you so much for your time and for your generosity.
It really has been enjoyable for me getting to know you.
And I look forward to meeting you in person at the upcoming World Medical Innovation Forum.
Thank you, Rick.
And if you want to do this again, I'd be delighted.
