Last updated July 1, 2022, by Lindsey Shapiro, PhD
✅ Fact-checked by Inês Martins, PhD
What is Tcelna for MS?
Tcelna (imilecleucel-T) is an investigational treatment that has been tested in clinical trials for the treatment of relapsing forms of multiple sclerosis (MS).
The cell-based therapy, formerly known as Tovaxin, received fast track designation by the U.S. Food and Drug Administration in 2011, which was expected to accelerate its development and review for secondary progressive multiple sclerosis (SPMS).
However, Opexa Therapeutics, the company developing this medication, discontinued its clinical program of Tcelna in 2016 following unsatisfactory results in a Phase 2 trial.
How does Tcelna work?
MS is caused by a mistaken autoimmune attack on myelin, the substance that surrounds and protects nerve cells. A number of immune cells are involved in this attack, but one of the major drivers of disease are a set of inflammatory T-cells that are primed to attack myelin.
Tcelna is a vaccine designed to reduce the number and activity of myelin-reactive T-cells. The components in the vaccine are tailored to each patient’s immune response against myelin.
To develop the personalized vaccine, researchers first evaluate a person’s immune reactivity against 109 peptides (small proteins) found across the three key myelin proteins — myelin basic protein, myelin oligodendrocyte glycoprotein, and proteolipid protein.
A personalized version of Tcelna, containing the most important peptides involved in that individual’s immune response against myelin, is then manufactured using Opexa’s proprietary ImmPath technology.
In a final step, researchers collect immune cells from the patient and grow them together with the selected peptides, creating a pool of cells that resemble the patient’s own myelin-reactive T-cells. These cells are then inactivated via irradiation, and infused back into the patient, where they will be seen by the immune system as harmful. This results in an immune response against the myelin-reactive cells, which is expected to restore immune regulation.
As the targets of immune responses may change over time, a new, personalized version of Tcelna is developed for each patient on an annual basis.
How was Tcelna administered in MS?
In clinical trials, Tcelna was administered as a subcutaneous, or under-the-skin, injection containing six million to 90 million cells. Patients received five of these injections per year.
Tcelna in clinical trials
Five clinical trials have investigated Tcelna in a total of 356 patients with relapsing forms of MS, many of whom received multiple years of treatment.
After initial studies demonstrated the safety and feasibility of T-cell vaccination in people with relapsing-remitting multiple sclerosis (RRMS) and SPMS, Opexa launched a Phase 1/2 trial (NCT00587691) to examine ascending doses of this therapy, given via four subcutaneous injections over 20 weeks.
Results showed that the dose containing 30 million to 45 million cells was the most effective, leading to a 92% reduction in myelin-reactive T-cells after five weeks, and a 65% reduction after one year. Regardless of dose, patients experienced significant reductions in relapse rates and tended to have slower disability worsening, although this last measure did not reach statistical significance.
TERMS trial
The Phase 2b TERMS trial (NCT00245622) evaluated the safety, tolerability, and efficacy of Tcelna in 150 people with RRMS or clinically isolated syndrome. Patients were randomized to receive the T-cell vaccine or a placebo, given via five injections over a one-year period. Injections contained 30 million to 45 million cells and were administered monthly over the first four months, with a final injection at month 6.
The study did not meet its primary goal, with patients in either group showing no significant differences in the number of lesions with active inflammation after a year of treatment.
However, a subset of patients with more active disease — those with more than one relapse per year, on average — saw disease-related improvements. This group of patients experienced reductions in their disability scores (meaning less disability) when treated with Tcelna, compared with worsening disability in the placebo group. They also showed a trend toward reduced relapse rates.
Tcelna was generally safe and well-tolerated, with no reports of serious side effects and no patients discontinuing due to side effects.
An open-label extension of TERMS, called OLTERMS (NCT00595920), was initiated but terminated due to financial constraints, and no efficacy data were reported.
Abili-T trial
A Phase 2b trial called Abili-T (NCT01684761) was launched in 2012 to determine if Tcelna could reduce neurodegeneration in people with SPMS. A total of 183 patients were enrolled at sites in the U.S. and Canada and treated with five annual injections of Tcelna (30 million to 45 million cells) or a placebo, for two years.
The trial’s primary goal was to measure changes in brain volume, a measure of nerve cell death. A secondary measure was the proportion of patients with sustained disability worsening at three and six months.
While Tcelna showed a favorable safety and tolerability profile in the trial, it did not prevent brain atrophy or slowed disease progression, failing to meet its primary and secondary endpoints.
Common side effects of Tcelna
The most common side effects related to Tcelna treatment in MS clinical trials were reactions at the injection site. These reactions were mostly mild and included bruising, discomfort, redness, and swelling.
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