Author Interview: Doctor Carlo Tur, February 2026

0:00Hello, everyone, and thank you for joining us for what I hope will be an interesting and informative discussion around some of the hottest data in rheumatology. My name is Recepter Nash and I'm a beautiful downtown Brisbane with the University, and today I'm delighted to be joined by Dr Carlo Toua from the Department of Medicine through rheumatology and immunology, the Friedrich Alexander University in Urland and Germany. It's my pleasure to have you to join me today, Dr Toua, to discuss one of your recent papers published in the Annals of the Romantic Diseases, and we're looking at the effects of different B-celled-the-pleeting strategies on lymphatic tissue. B-celled-the-pleation will be one of the hottest topics in rheumatology at the moment, following all the excitement with CAR-T therapy, and that a lot of this work and the original pioneering work

1:02has all come from Dr Shets Unit in Urland, and this particular paper looks at a number of B-celled-the-pleeting options, including retaxamab, which you've been using for a long time, benetubamab, which is a monoclonal antibody, open-etusamab, another one that's now available in being used in oncology, and comparing it to CD-19 CAR-T therapy, and we're getting approached weekly by companies to do these phase one studies with new molecules, and B-celled-the-pleation is the hottest topic in rheumatology, lupus, myocytus, scleroderma, etc., acovascularitis, and now we even act for positive rheumatoid arthritis. Welcome, Carlo, tell us a little bit about yourself first, your background, and what you're working on at the moment in your interest plays. Hello, Peter, thank you for your introduction.

2:05My name is Karl Puerh, I'm a rheumatologist, and currently in 2023, I joined the group of Professor Schett in Atlangans, and started assessing the effects of different B-celled-the-peating strategies on the T-shirt, in particular, in Atlangans we established a biopsy unit, including sampling of angular lymph nodes, and this allowed us actually to assess different effects of different treatments on the lymphatic tissue, and this is actually my main topic at the moment. So, just tell us what you tried to do with this study. You looked at the depth of B-celled-the-pleation, and you made a score, and you included histology of an angular node, done twice a number of months apart, but before the B-cells had come

3:11back. So, tell us a bit about this technique of lymph node biopsy. Is it something that is going to stay very much research, or could it have a wider application? Yeah, that's actually a very good point. Actually, what we believe is that the lymph node sampling could actually also be as an important clinical tool to also monitor the effects of the treatment, and also tailoring, then personalizing the treatment, since it is actually, we have performed in a lung in the moment almost 200 biopsies since almost three years now, and we do that on a routinely way, so it's quite an established technique at the moment, and it can be implemented also in the clinical practice.

4:14This is what we believe, and can actually assess the depth of B-celled-the-pleation in the tissues, and then guiding then the treatments. So, you use an ultrasound to find the nodes, and you can repeat B-cell in the same node itself? Yeah, actually, it's a mini-basif technique, which we, it's all ultrasound guided. We use a needle, the same core needle, a 16-gosh core needle, which is the same that is usually adopted for the same obvious biopsies, and we then retrieve pieces of the Inglina lymph nodes or percutaneously. And you've done a couple of hundred, is there any sampling error type issue, or does, because you look not only at B-celled-the-pleation, you look at lymph node structure,

5:17so if you did two biopsies from the same node, would you, at the same time, would you get very similar results, or would they be, there might be sample error there? Yeah, actually, we take more than than one piece, but we, we showed actually, and especially with CAR-T cells, the result are quite consistent, so now all of the patients who got a lymph node biopsy, then showed a complete B-celled-the-pleation of the CD-19 CAR-T cells, with the, with the protein-base B-celled-the-pleaters, sometimes it happens, is this not, anyway, as consistent as, with the CARs? All right, so let's talk about what you did. You took a relatively small number of patients, 20-on patients, maybe four in each group. Just explain the groups to those people who are not familiar with the different B-celled-the-pleases that you looked at. Yeah, actually, so the total number of patients was 24, divided in four small groups. Twelve

6:23patients were allocated in the CD-19 CAR-T cells, and actually five of these patients were already part of a, of a previous publication, and while the other 12 patients were split it into the three different treatment groups, we compared, you know, Tutsu-Map, which is a glycogen-eared CD-20 monoplonal antibody, so a class II antibody, CD-20 monoplonal antibody, and then Blinatumumap, which is a CD-19 CD-3 B-specific T-cellingager, which is also alone from hemathone ecology, and then we compared them also with the standard of care as a protein-based B-celled-the-pleaser, which is retooks him up, which is a type I monoplonal antibody, so in each of these three groups were four patients with different autoimmune diseases compared then with 12 CD-19 CAR-T cells.

7:29Now, the CAR-T patients, of course, got lympho-depletion with cyclophosphamide and redarabine, and we've always wondered, does rheumatology need the lympho-depletion, like the malignancy patients, the lymphoma patients do, particularly as the redarabine's genotoxic, and we're talking about young women who go on to have, you've already had a couple of normal pregnancies, do you think we need lympho-depletion? Actually, there are some studies on point with the reduced lympho-depletion as well. What I can say is that from our point of view, for example, we don't believe that the lympho-depletion can actually affect the depth of B-celled-depletion, and indeed we had one case with the patients who received up to two grams of cyclophosphamide just before treatment with

8:35Obeno-to-zoom-up. And we show, and we perform, then the baseline, a live C-before Obeno-to-zoom-up, and we saw that actually there was no effects on the B-celled-depletion, the B-cell count. So, the B-celled numbers were still present, not affected by cyclophosphamide. Excellent. So, just to fill it in, re-tuximab, they've got a gram twice, two weeks apart, CD-20, glycosolate, or few-cosolated CD-20 Obeno-to-zoom-up, also got a gram twice, two weeks apart. Blinatubemab, the T-cell-engager, which binds T-cells, and does it bind to CD-19 or CD-20? CD-19. CD-19, and then it makes the T-cell, if you like, kill the B-cell. That's given over a continuous infusion over four days. So, that's being used in oncology,

9:37but maybe not quite so practical in rheumatology, and then of course your normal CAR-T, where people are lymphoid depleted, and then you've stopped all their therapy prior to these treatments, but they did get a lot of treatment before. Do you think any of the treatment like the OB group got some re-tux before? Do you think it affected the biopsy results, or are they too long in the past? Yeah, we do believe that, because for example, in Blinatubemab patients, we see some actually some affection already, some reduced scores in this follicular architecture score that we built, and this could be probably an effect of a previous exposure to re-tuximab that all of these patients had. So, there could be a cumulative effect that can be considered, but still this was not sufficient to reach a deep B-cell depletion,

10:43a complete eradication of the B-cell compartments. Okay, so anyone who wants to have a look at this paper, this is a fantastic histology in figure one in particular, and what striking to me, and I'd love your comments, post CAR-T, you've eliminated all the B-cells, and you've got rid of the lymph node structure, whereas re-tux, there's a lot of B-cells left, in particular a lot of CD-20 B-cells, positive B-cells left, so re-tux might peripherally deplete, but the problem is it doesn't do a lot of deep tissue depletion. Blinatubemab somewhere in the middle, where there's good removal of CD-19, but there's still some CD-20 hanging around, and even post OB looks very good. Openatubemab looks very good at CD-19 removal, and even quite good at CD-20 removal. Can you fill a sin on that beautiful picture, because it looks like OB is not so bad, at least compared to re-tux, and compared

11:51to CAR-T. Yeah, actually, this is the point that we were surprised to see that actually OB no-tuxemab, but this is actually confirmed also some of the preliminary studies that it has and made sure depletion compared to re-tuxemab probably thanks to the fact that it relies more on the antibandidependence site of acesity instead of complement dependent site of acesity, which is the main mechanism of re-tuxemab. So it looks quite powerful, but still, and indeed, it actually managed to reach a full eradication of these in one of the four patients in our study, but still, so it has the potential, probably, to reach a cell-based light effect, like the CARs, but it doesn't reach the same consistency of the cell-based therapy.

12:57And what about the effect on lips-known architecture? OB? This is also something very interesting that was a surprise when especially when we performed the first study, we first witnessed to this big change in this eradication of the follicular network, including the FDCs and the T follicular helper. So it seems that the follicular network really relies on the presence of B cells, because the expression of CD-90 in follicular dendritic cells is not very descriptive in the literature. There are only some very old claim about that, but which is most likely is that there is a mutual signaling between B cells and follicular dendritic cells and T follicular helper that gives them alive somehow. So this was something really intriguing.

14:03So the reason why I'm popping on about OB is because rheumatologists are very used to infusing retoxamam. Access to a daycare center, doing it in your own clinic, we're quite used to it, and I kind of think of open-to-toes of members as a supercharged retox if you like. And so I'm interested in how the depth of depletion and the effect on architecture, because for us, practically, parties tricky because withdrawal treatment, and some patients flare, give them lympho depletion, and then they need eight days in a hospital bed, utropenic. Half of them get CRS needing tosyllizumab. Fortunately, I can just very uncommon. We need to involve GMCSF, for hematologists, infectious diseases, that makes life very tricky. Access to hospital beds is always a nightmare. But if you could have something that's really pretty effective, like open-to-toesimabs,

15:06looks like in your study, that'll be much more practical for people to do. As far as CRS is concerned, did you see any reactions or issues or CRS in the open-to-toesimab patients that you've been treating? I will actually, on this bottom, I mean, the safety profile would say that it's quite overlapping the retoxymab. So at that point of view, I would have less concern compared to the new treatment that I've been trying at this moment. And to be fair, the volume of B cells is quite small compared to a lymphoma, so you wouldn't expect major stuff. The other thing that I found very curious, looking at that beautiful figure, is a lot of CD-20 staining left when the CD-19s gone. And we've been approached

16:08by a bi-specific T-cell-engager that blocks 19 and 20. Do you think it's important to take out 20 if you're taking out 19? Yeah, I mean, on this one, I have also to point out that, of course, these different staining have different sensitivity. So CD-19 usually is worse than CD-20 in the staining, so there could be always some kind of discrepancy between the staining in terms of self-identifications. Of course, I mean, what CD-19 allowed more compared to the CD-20, this is more expressed on a larger number of B cell precursor within the B cell differentiation and especially what is important, I would say, is that CD-19 is also expressed on plasma blasts,

17:14which could be one of the driving characters and pathogenesis, for example, of lupus. So I would still say that CD-19 is a very good target and that should take into consideration. So that's a very important point that you make there, because we were always taught by Georg at his lectures, ACA ULA, that it's best to leave the plasma cell alone, because that's your protection against COVID, Canada, tetanus, pneumococcus, etc. And by taking out CD-19, you're leaving the plasma cells alone, but I noticed in that nice paragraph where you talk about the reduction in various cells, there's about a 50 plus percent reduction, 58 percent reduction in plasma cell numbers with CAR-T therapy, which I thought you had to have BCMA as your target if you want to take out the plasma cell. So is that because this is not as straightforward and

18:20simple as we thought, and there's a lot of shared receptor expression across these cells, and it's not specifically just CD-19 takes that up to the plasma blasts and stops. Yeah, yeah, absolutely. I mean, we don't have to consider this, the different B cell subtytes as static cells, so probably the expression of the different antigens on the surface change this very dynamically. It's some express them more, some express a little bit less, but probably the reduction that we see in that case is, it has to be referred to a portion of plasma blasts, which are still, which are already expressing CD-138, but still retrieves some CD-19, and that's why they get killed by a CD-19 CAR-T cell. So you did two biopsies, roughly 70 days apart

19:21before the B cells returned. Tell us a little bit about what you found, peripheral blood in the tissue, immunoglobulins, those kinds of things. Yeah, so we, the peripheral blood, we used as a reference to decide the time point by which performing the follow-up biopsy, because, of course, we started for the consensus to make them almost renewed since they're, of course, different pharmacokinetics and pharmacodynamic a common point to decide when performing the follow-up biopsy was, where they all achieved a complete B cell depletion in the peripheral blood. But this was the case, actually, for all patients, but for two plinatumumab patients, since plinatumumab is a very short half-life. So one of these patients actually never reached

20:23a complete depletion in the peripheral blood, and the other one, it reached it, but then a recorded earlier compared to the others. So all of the biopsies were performed when a peripheral depletion was present, apart from these two patients. And regarding the immunoglobulin, we, we see a decrease of IgG in all groups, but in all of them, this is more pronounced in the in the CD-19 CAR-T cells, but never, they never go down under the threshold for the immunoglobulin substitution. And for the IgM, this is consistent, probably, with the depletion of of plasma blasts for antibody, I mean, early antibody producing cells, they go a bit, a little bit more down compared to the IgG, but because we are depleting the machinery that is producing

21:26the immunoglobulin, so it makes sense for the IgM. Do you see any changes in T cells or in myeloid cell numbers? We wanted to assess that as well, of course, no actually those compartments were not affected by none of these treatments. And the clinical responses that you saw in these patients added, they respond to their treatment when you compare the four across. Yeah, this is also another important point, of course, it is, even thus more than a number of patients, it's hard to solve conclusion. But what it's quite striking to see is that patients who receive CD-19 CAR-T cells, they all received a free drug remission and a major response while the patient with a protein-based B cell, the pleaders may have reached a major clinical

22:32response and also remission, but a further administration of the treatment was necessary in order to avoid flares of disease. By further statement, you mean the traditional microphenolite and other things, or do you mean repeat those of the pleader? Because the B cells came back and you could see activity? Yes, actually, or because they actually never reached a complete remission, so they received a significant clinical response, but not so was not safe to withdraw the treatment actually. Sometimes we also got back then to a standard treatment. I see. And one of the questions is how safe it is to retreat with the molecules. You didn't see an immunogenicity in this very short period of time that you followed these patients.

23:33No, but as you say, it's a very short time to see that. And in your experience with all those a couple of hundred other patients, have you had to retreat with some of these molecules over time and you're not seeing an issue? Yeah, it happened. No, we didn't see an issue. Okay, so just a comment on changing structure. How important is it for remission that the lymph node structure be changed like it does in CAR T therapy? Actually, I think that this dramatic changes simply reflect the depth of E cell depilation. So this is important as with to in order to achieve this so-called immune reset, we probably have to eliminate all the reservoir potential reservoir of out of reactive clones.

24:37And since this eradication, also the follicular structure is strictly connected to a DB cell depilation, I think that this is quite crucial. But the important thing that actually after for example, we did then a late follow-up pipes is after one year and the lymph node comes back and also its architecture comes back as a completely normal one. And with CAR T, does it come back? Yeah, yeah, absolutely, yeah. And the B cells return, but they're naive, not auto-reactive B cells. Okay, and so any comments you want to make finally about your study, what you intend to keep going to do next with this study? Yeah, we are currently studying more in depth the immune cell compartment, not based only on immunostochemistry, but also assessing the changes

25:41of different immune compartments with the special proteomics and transcriptomics. And this is quite exciting because there are very interesting insights, but this would be for the next show. And can you give us your rating? CAR T is the best and protects the worst and blinny in the middle and OB not too bad. How would you rate these four drugs for the clinician moving forward? Yeah, I mean, I would say the CAR T cells are the best, but of course there are a lot of cons that we have to consider. Retoxymab has been a very good action star for many years, maybe it is time to retire and leave the stage to open a Tutsumab, which is a very good

26:43opportunity. With Blina, with Blina Tutsumab, we probably have to get more data and also to adopt a dosage now and to have more cases on that. And now looking into your crystal ball, we did the original retox studies where they got six monthly retox out to five, six, seven years and we saw not only the IgM disappear, so the rheumatoid factor went away, but then the IgG started to drop and they started getting infections and we had to start giving them gamma globular. Do you predict that repeating doses of something like OB and Tutsumab is likely to do the same thing, end up knocking gamma globulans down over time? Yeah, I think that this is, yeah, it's predictable,

27:45yeah, I mean, it's quite straightforward, I would say, yeah. Take a message from the clinician, from your beautiful study. TSU is becoming always more important also to understand if this new treatment are effective, so the blood on which we, the peripheral blood, on which we relied for many years, which is of course, it's more easily accessible in the clinical routine, but we have to look deeper also into the tissue. So thank you again for your time, I greatly appreciate it, Dr. Tours. If you'd like to know more about this paper and others uploaded to the immune mediated inflammatory disease forum website, you can get detailed slidesets available at imidforum.com.

28:50Please subscribe to this podcast, Spotify, iTunes, other podcast media, let us know what you think, you can watch us on the immune mediated inflammatory forum on YouTube and finally, you can follow us on Twitter or ex-linked in Facebook to keep up with all the new inflammatory disease content that's coming soon across specialties, gastro-derm room. So thank you again for your time, greatly appreciated and we'll be looking forward to see where your work goes next. Thanks very much, Carla. Thank you. Bye. Bye.