Offering a wide array of functions and structures, and affecting multiple physiological systems, Biologically Active Monoclonal Antibodies have been instrumental in biological/cellular assays for recognizing cytokines, chemokines, CD antigens and proteins. Whether they are utilized to trigger, neutralize, enhance, activate, induce, inhibit, or characterize, they help to explore the frontier of new mechanisms of action. In the last few years, therapeutic antibody drugs have gone through an explosive growth with more than 20 antibody therapeutic drugs having received FDA approval in 2017, and even more importantly there are more than 300 clinical trials currently ongoing exploring treatments that show promise in everything from the area of cancer treatment to psoriasis, and to multiple sclerosis.
In exploring this topic, Dr. Anne Sloan of Cell Sciences discusses where and how this new group of monoclonal antibodies is being used in research today.
Q: What type of work do you do with biologically active antibodies?
Myself? Not much, however I do supply them to researchers who are doing laboratory work. At Cell Sciences, we supply a wide range of these antibodies that have been specifically designed for researchers exploring certain mechanisms in the human body. Eventually, these often lead to the development of drug targets, however, I am usually supplying these antibodies to researchers in the early stages of that research, in the in vitro stage.
Q: Why is now such an interesting time for research utilizing Biologically Active Antibodies?
I think, in general, there have been a series of advancements technologically speaking that has allowed not only for better identifying and delineating the possible mechanisms of action – especially in cancer, but also in exploring points of intervention – and of course, having substrates and inhibitors for experiments to explore the mechanisms at work is vital. In the end, the research continues to become more refined and it is our job to stay on top of the research and have the products along that journey available to test and challenge the researchers hypothesis and theories.
Q: Can you tell us some of the fascinating areas that are being investigated?
Well, sure. I mean, obviously the specifics vary – but the general areas – definitely. IL-23 [Interleukin-23] has definitely become a really interesting target for moderate to severe psoriasis. There are 3 different monoclonal antibodies that selectively inhibit the IL-23p19 subunit – guselkuman, tildrakizumab, and risankizimab. This is really exciting because, in fact, this isn’t necessarily a new target – it was on the shared IL-12/23p40 subunit. It was really promising for psoriasis however there were some safety issues with cardiovascular risk. This new approach is separating this subunit and being able to preserve the IL-12- mediated Th1 response and just inhibiting the IL-23p19 subunit. It is great because the clinical trials have shown some really impressive results. IL-17A and F, another participant in the inflammatory cascade involved in the lesions has been another target for psoriasis at the receptor for IL-17 – and that is showing some incredible results with total disease clearance with brodalumab and ixekizumab.
Let’s see – IL-4 and IL-13 are critical to the induction and perpetuation of the Type 2 response and have been implicated in multiple atopic diseases – asthma, chronic sinusitis, and allergy. There is a drug [dupilumab] for atopic dermatitis that is targeting the receptor of IL-4 to inhibit the signaling of IL-4 and IL-13 to cells that express the receptor. But this is a great example… it is an area that is being wildly investigated because there is a lot of potential within these mechanisms that are being elucidated.
Q: So there must be a lot of these antibodies that are multifaceted – as in they are being targeted for multiple conditions?
Well, yes. I think it is important to not just focus on the drug per se, but really the mechanisms that are being explored. When you are thinking about a disease like cancer – you will be looking at these mechanisms such as apoptosis and the different pathways to see about how that physiological mechanism can be exploited albeit through TRAIL [the TNF-related apoptosis-inducing ligand] or the Fas or FasL induced apoptosis. The exploration of these pathways is what is really exciting – trying to break into the potential of what understanding these mechanisms could actually mean – ultimately to be able to manipulate these processes to our benefit.
I think you can also think of something like CD20, which is expressed on virtually all of the stages of B-cell development and who to the best of our understanding is there to optimize the B-cell immune response. There are multiple anti-CD20 mAB drugs approved [ofatumumab and obinutuzumab] or in the pipeline [ublituximab] for chronic lymphocytic leukemia – but CD20 is a target that is also in the pipeline for multiple sclerosis [ocrelizuman]. And of course, as the immune system’s B cells get implicated, the role of CD20 is going to be better understood and already we are seeing links suggesting it has a role in diabetes [mellitus] and obesity and that connection and the cascade of those effects – hypertension, arteriosclerosis, et cetera. But what we do know is that we don’t know it all yet… and so the puzzle pieces continue to come in. And that is really common. Sometimes you see drugs that make it to market but then they are pulled back like catumaxomab – which had been approved and was targeting EpCAM and the T cell co-receptor CD3… but it was just withdrawn this last year – so there is still a lot that is being defined in these mechanisms and a lot of these treatments still need to continue to be worked out on the bench for improvements to be made. So it is always this work in progress.
Q: Do you have any favorites coming down the pipeline or are especially noteworthy?
<laughing heartily> No, actually. I am rooting for them all; let’s just say that. I think it is fascinating to see pictures coming together. So for instance, exploration into T-cell activation began decades ago – but with new technologies and abilities on the bench – the mass of ligands and antigens CD28, CD80/CD86, CTLA-4 – the whole lot has began to get sorted. It is exciting to follow these advancements since being a student and now there are drugs in the pipeline (tremeliumab, durvalumab) that may offer alternatives to chemotherapy for patients (with non-small lung cancer). That’s amazing.
I also love to hear about these really novel targeted approaches. For instance, there is a new drug [emapalumab] targeting IFN-gamma. It’s working to treat hyperinflammation – with very severe conditions like primary hemophagocytic lymphohistiocytosis – which is this condition that activates T lymphocytes and macrophages and is fatal if it is not treated. So… it gives me hope when I see research fields begin to collide at a higher level of understanding – the genetics, the immunology, and then drug development. Oh and CD4. I think that is being targeted now [ibalizumab] for [multi-] drug resistant HIV [human immunodeficiency virus] infection. It’s great. So maybe I do have some favorites – no, not really. There are a lot of exciting areas of research and this group of biologically active antibodies and clones that we are offering and working with are linked to some great research that is being explored with some incredible research groups leading the way. To be honest, I’m just a bit of a science nerd and am lucky enough to follow along with the incredible strides of some great researchers.
Cell Sciences offers a wide range of Biologically Active Monoclonal Antibodies that are preservative free and carrier free. A few are listed below, but you can view more of our Biological Active Antibodies here.
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