Multiple sclerosis: the first trials with Car-T therapies begin

Multiple sclerosis: the first trials with Car-T therapies begin


2024 is the year in which Car-T therapies against multiple sclerosis will be tested for the first time: a handful of centers – in the USA, Germany and China – have in fact just begun to enroll the first patients, for three different phase 1 trials (the first step of clinical research, which aims to provide an initial evaluation of the safety and tolerability of a possible therapy).

What are Car-T therapies

Car-T are immunotherapies that are based on the patient’s own cells which are taken, genetically modified in the laboratory and then reintroduced into the bloodstream. This is why they are also called ‘living drugs’. We learned about them over 10 years ago, with the studies of Carl June of the University of Pennsylvania and the story of Emily, the first child to receive Car-T therapy for a leukemia resistant to all other treatments. Since then, over 20 thousand people have been treated with CAR-T therapies worldwide. Specifically, the cells used are T lymphocytes (a particular type of white blood cell), which are modified so that they express the CAR molecule on their membrane (acronym for Chimeric Antigen Receptor): thus engineered, these T lymphocytes become capable of recognizing and bind to a specific “target”.

From blood cancers to autoimmune diseases

Which target? In most cases, the CD19 antigen is targeted: a protein present on all B lymphocytes, i.e. the cells that proliferate uncontrollably in many blood tumors. And B lymphocytes also play a crucial role in the onset of various autoimmune diseases, in particular lupus erythematosus and dermatomyositis. Hence the idea of ​​using Car-Ts in this area: the first clinical trials started in 2017 and in Italy the Bambino Gesù Hospital in Rome has recently announced the first encouraging results from the treatment of three young patients, two with lupus and one with dermatomyositis.

Three trials in multiple sclerosis

Now the hope is that Car-T therapies could represent a new frontier also for people with multiple sclerosis. According to the registry clinicallatrials.gov (where the trials are carried out at a global level), three clinical trials are starting in February: a multicenter one in several hospitals in the USA and some European countries (among which, to date, Italy is not included) promoted by Juno Therapeutics (affiliate of Bristol Myers Squibb); one in a single center in the USAthe Stanford Multiple Sclerosis Center, promoted by Stanford University in collaboration with the company Kyverna Therapeutics; one in Chinapromoted by the RenJi Hospital in Shanghai with the company AbelZeta Pharma Inc.

Advances in multiple sclerosis

“Multiple sclerosis is the neurological disease for which we have had the greatest therapeutic progress in recent years – comments a Health Roberto Furlanmember of the Scientific Committee FISM (Italian Multiple Sclerosis Foundation) and Director of the Institute of Experimental Neurology, Division of Neuroscience at the IRCCS San Raffaele in Milan – Today we have around twenty molecules, one more effective than the other, for the relapsing-remitting form. The problem exists when the disease arrives in its progressive form. We know, in reality, that these are not exactly two different forms, and it is thought that the mechanism underlying the progressive phase is present from the beginning of the disease. The hypothesis that is now being put forward is that Car-T therapies may represent a more effective strategy than the monoclonal antibodies used so far, which are directed against another target, CD20″.

The “targets” of therapies: CD20 and CD19

To understand the possible rationale of the Car-T strategy in multiple sclerosis we need to take a step back. Let’s imagine the life path of a B lymphocyte. “It goes through different stages of maturation and in each phase it expresses different markers, including first CD19, and then CD20 – explains Furlan – Targeting CD19 potentially means hitting B lymphocytes when they are ‘younger’ and, always potentially, therefore achieve their more profound elimination. This strategy actually seems to work well in autoimmune diseases such as lupus, where B lymphocytes have a very important role as producers of auto-antibodies, i.e. antibodies directed against our own tissues. It must be said that in multiple sclerosis the role of auto-antibodies is not as important. Furthermore, we have already tested monoclonal antibodies (which are much simpler drugs than Car-T, ed.) directed against CD19 and so far they have not shown particular advantages compared to those directed against CD20, used in clinical practice. It must be said, however, that for their part, Car-Ts theoretically have the possibility of reaching brain tissue as well.”

A proof of principle

Assessing the toxicity that Car-Ts could develop at the brain level and their safety is one of the most important aspects of the ongoing clinical studies, as explained to Nature News Mark Freedmanneurologist at the University of Ottawa, pioneer of stem cell transplants and consultant to BMS, e Jeffrey Dunn from Stanford University, which is conducting the Kyverna Car-T trial in California. “From a purely scientific point of view, these new studies can represent a very interesting proof of principle – concludes Furlan – which could first of all shed light on some questions that are still unanswered”.



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