We've Got To Talk About CAR T Cells Save

My name is Jus Yousuf. I'm a consultant rheumatologist from Leeds, United Kingdom. I'm reporting for RheumNow live from Vienna, Austria. Today is day two of EULA conference. There have been many abstracts presented.

So one abstract that I would like to discuss is about the progress of CAR T cells. So in this conference, there have been so many advance pertaining to CAR T cells. And if we don't talk about CAR T cell, it probably means that you've not attended this Congress. And so just to summarise quickly in terms of CAR T cells. So these treatments have been thoroughly evaluated in the context of haematological malignancy.

But from the perspective of autoimmune diseases, these treatments were introduced about two years ago by Professor George Shed's team, for which, they, demonstrated successful outcomes of PIE-five patients with refractory SLE, who responded brilliantly and with good clinical outcomes, as well as drug free remission. So we're rolling forward two years now to 2024. There have been many interests by pharmaceutical companies in producing the CAR T cells. So just to recap in terms of the process, so CAR T cells stand for chimeric antigen receptor. So the principle, is to induce profound B cell depletion, and hopefully will then reset the aberrant immunological abnormality.

So what they do is initially infuse patients with strong chemotherapies to induce profound depletion. And after that, the blood samples from the patients were taken for which the T cells were extracted in a process called apheresis. Then these T cells were then, re engineered in the lab, to produce a protein on the surface, which then respond to specific receptor. And the most common receptor will be the CD19 so that when these then re infuse to the patients, they can attack cells, the pathogenic B cells. So at this EULAG Congress, there is now a novel approach in terms of attacking two receptors, so not just CD19.

So this is what we call it compound CAR T cells. So using a double approach of attacking two receptors. One is CD19 and one also BCMA. And the logic to attack the BCMA is because BCMA will express on the specific B cells, particularly the plasmablasts and also long lived plasma cells. And this will result in pathogenic autoantibodies elimination.

Okay, so basically, regarding to this abstract, so this was a phase one open label trial in China. So, the presenters presented data of 12 patients all had severe refractory lupus nephritis. All of them had a prior renal biopsy, which showed a range of classes from class three to class five. And all these patients underwent the treatment and the result was outstanding in that the majority of patients had profound clinical response in terms of reduction in proteinuria, and majority of them reached the complete renal response rate, which is proteinuria level at less than 0.5 gram a day, and the patient were drug free remission as well. And the data were presented for follow-up just over two years.

So people were asking as well, what happened to the infection risk? So because of the depletion of the plasma blast and also long lived plasma cells, People are concerned of this, but the data, the initial short term data showed minimal infections apart from mild COVID. There was one mild urinary tract infection observed. So, this novel compound approach appears to be showing early efficacy and safety and is planned to be developed in later stage of the trials. So in terms of, how, this is relevant to clinical practice.

So, in this Congress, there have been quite a few other CAR T cells data which were investigated in phase one open label trial. I think the key thing is about selection of patients because what do people mean by severe refractory lupus? How refractory is refractory? Does it depends on how many biologics that you've been undergoing or potentially maybe when you've tried, B cell deep breathing therapy such as rituximab and people did not, reach, complete depth of depletion. So, these patients could be considered, refractory.

So, yeah, so this is still in the debate, but also other important factors including safety, because this C compound have only just over twelve months period of follow-up. And even in Professor George Shat's cohort initially, the follow-up was up to two to three years. So we needed more longer term data because we don't know what happened after the B cell have returned. So potentially later down the years, then it may bring a disease relapse and what happened then? I mean, we going to give another CAR T cells therapy which potential significant side effect and etc.

So, these are all questions that's still up in the air. But certainly, you know, there has been a lot of interest in terms of CAR T cells therapies, not just in SLE, but also in other across ANA associated autoimmune diseases. I hope, you found my summary interesting. And please follow me, and also RheumNow on social media outlets for more coverage of EULA twenty twenty four in Vienna. Thank you.