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AAPS 2023: interviews from the floor with Dominic Warrino
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AAPS 2023: interviews from the floor with Dominic Warrino
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Upload Date:
2023-12-18T00:00:00.0000000
Transcript:
Language: EN.
Segment:0 .
DOMINIC WARRINO: My name is Dominic Warrino. I'm the Senior Director of Scientific Services at KCAS. I've been at KCAS for close to 11 years. I've been in the bioanalytical CRO space for a little over 17 years and I've been in the immunology, gene therapy, and biomarker and pharmacodynamics space for close to 30 years. My first job out of school was doing autologous T-cell therapies for the treatment of metastatic renal cell carcinoma patients using a monoclonal antibody, so everybody else was kind of studying small molecules and other things and I found myself doing cell and gene therapies at a very young age in the mid-90s.
DOMINIC WARRINO: I joined the PK focus group about 6 years ago now, and I've been on that group for the last 6 years. It's been a wealth of information. It's an incredible opportunity to be able to help service our clients and learn more about the PK space, share what we're doing at KCAS, learn from others. It's a great resource. I'm also a member of the cell-based NAb assay group, I'm a member of the data management group, I'm a member of the liquid biopsy group, and, as of this year, I'm co-chairing the critical reagents group, which started in January of 2023 of this year, which has been an eye-popping experience about how much effort goes into leaders of those things, but it's been a fun ride and I really enjoy working with AAPS.
DOMINIC WARRINO: In the early days, when we were doing these autologous T-cell therapeutics, people were still unearthing parts of the MHC and how that all functioned. We were really working in what I would call a black box. Immunology was still somewhat of a mystery at the time, in fact, you couldn't get an immunology degree until, I think, 2004 or '5 is what I have, and that was one of the first immunology programs and that was at the University of Pittsburgh School of Medicine.
DOMINIC WARRINO: And so we had flow cytometry, but we didn't have things like ELISpots, and we didn't have really the tools that you have today to monitor autologous T-cell responses. Also a big change has been in the genetic component of it, so now they've found ways to kind of re-engineer the T-cell receptor. That's what-- and now it's evolved into B-cell receptor, it's evolved into NK-cell receptor.
DOMINIC WARRINO: All of that has been something that-- it's been wonderful to watch over the last 30 years to see how initially, we were kind of like I said, working in that black box, and now they've got targeted responses, they've got ways to knock down the immunogenicity of CAR T-cells, they've got ways to hone them in. It's just been an unbelievable ride. Also, the manufacturing of them has become something where the cost for it is still a little bit cost-prohibitive, but there's a lot of new technologies out there that help with making it so that you don't need a clinic on every corner to do a CAR T-cell therapy.
DOMINIC WARRINO: I think as we look at the bioanalytical space and even like emerging technologies or drugs of the future that are going to be life-altering, life-changing, life-saving drugs, we mentioned CAR T-cells, but in the cell and gene therapy space itself, we all are aware of mRNAs and all that's happened with that, but that's led to a lot of therapeutics for rare diseases, immuno-oncology, and so those vector-based technologies are incredibly powerful.
DOMINIC WARRINO: People are finding new ways to package them in different types of particles, they found new ways to make them less immunogenic, they found ways to kind of-- what I think of is like make chimeric versions of them and they kind of cannibalize from certain AAVs, and they make them incredibly powerful, incredibly targeted. You do have to worry about on-target and off-target and some of that.
DOMINIC WARRINO: And then the other is the ADC space, which has really been a massive advancement in say the last 4 or 5 years about antibody-drug conjugates, or even any sort of like protein conjugate or-- people are using peptides and oligos, and putting payloads on that so the conjugate space, the chemistry around that. Some of the engineering is fascinating. We work on a couple of different-- we work on about eight or nine ADC programs at KCAS currently that are active, and two of them have very interesting engineering in them.
DOMINIC WARRINO: They have-- kind of like a prolytic form of it where the binding site of the antibody is blocked until it hits the tumor microenvironment. So that gives the ability of that drug and therapeutic to kind of circulate longer within the patient, until it finds the right spot where it needs to be. And then the activity of the drug becomes active in the tumor microenvironment, which is incredibly cool engineering.
DOMINIC WARRINO: And then there's others that are using click chemistry where you have a second payload that can be dosed to the patient to release the ADC. So the activity of that payload is inert until you give the second therapeutic, so kind of clever. Very challenging bioanalytically, ADC methods are-- to me, they're very challenging in that you have-- usually there's a couple of different PK methods that need to be developed and validated.
DOMINIC WARRINO: You have the immunogenicity portion, and often in the immunogenicity you've got domain specificity that needs to be assessed as well. But the two major advancements are cell and gene therapies and the ADC space. With that being said, I still think there's a lot of biologics out there like bispecifics and things like that, multivalent proteins that are very powerful, as well as the small molecules.
DOMINIC WARRINO: I don't want to discredit how many small molecules are being approved that still dominates approvals. So there's still plenty of small molecule, new entities in that space as well.
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