Elicera on CAR T-cells’ potential beyond blood cancer
CAR T-cell therapy is an emerging form of immunotherapy that has shown promising potential in, among other areas, various forms of blood cancer. However, this form of treatment has recently indicated additional areas of use such as in solid tumours and autoimmune diseases. BioStock contacted Elicera Therapeutics, Sweden’s only R&D company developing and evaluating CAR T-cells, to comment on the progress in the field.
In recent years, a new class of immunotherapy has emerged: CAR T-cells. This form of treatment has primarily been developed for the treatment of cancer. The treatment works by genetically modifying T-cells, a type of immune cell, to produce a chimeric antigen receptor (CAR) on their surface, enabling them to recognise and attack cancer cells. Currently, a total of six CAR T-cell treatments are FDA-approved, all of them targeting different forms of blood cancer. In addition, biotech companies are developing several hundred CAR T-cell treatments globally.
However, the development of CAR T-cell therapy has not been without challenges, mainly due to the high frequency with which patients relapse and the serious side effects that many patients experience. Furthermore, no CAR T-cell therapy has yet been approved for the treatment of solid tumours.
Read more about CAR T-cell treatment here.
Effect shown on ovarian cancer in mice
CAR T-cell therapies face two main challenges when treating solid tumours. The first is the heterogeneous expression of CAR target antigens, which increases the risk that some tumour cells escape the attack and instead form CAR T-cell-resistant tumours. The second challenge is local immunosuppression, which makes it more difficult for the T-cells to infiltrate the tumour, inhibiting their potential to kill cancer cells.
In February 2023, a study was published in The Journal for ImmunoTherapy of Cancer by researchers from the Karolinska Institute showing that CAR T-cell therapy demonstrated effect in mice with ovarian cancer, a solid tumour.
The study chose to focus on mesothelin protein, which is found on many ovarian tumours. The researchers tested three types of CAR molecules programmed to attack that particular protein. All three CAR –T-cells significantly extended the life of the mice with cancer, compared to those in the control group. But one of the three CAR-T types, called M1xx CAR-T cells, had superior efficacy. In the mice injected with that molecule the tumours shrank and they lived even longer than the others. Several of the mice were even cured.
Potential within autoimmune diseases
The potential of CAR T-cell therapy does not seem to stop at cancer. This type of treatment has also shown potential in autoimmune diseases, by selectively targeting and eliminating the immune cells that attack the body’s own tissues.
In autoimmune diseases, the immune system mistakenly attacks healthy cells and tissues, causing inflammation and damage. Current treatments for autoimmune diseases typically result in broad suppression of the immune system, leading to an increased risk of infections and other side effects. Researchers believe that CAR T-cells could become highly relevant for the treatment of autoimmune diseases through a more targeted approach. Currently, researchers are investigating the use of CAR T-cells to target specific immune cells responsible for the autoimmune response, while leaving the rest of the immune system intact.
Research in this area is already in full swing. A study published in Nature Medicine in the fall of 2022 investigated the effect of CAR T-cells in five patients with systemic lupus erythematosus, SLE. The study showed, among other things, that the treatment led to an improvement in clinical symptoms and a successful depletion of the hyperactive B cells, which are characteristic of the disease. All five patients achieved remission of SLE for three months after the end of treatment. It was well tolerated, with the most serious adverse event being mild cytokine release syndrome.
Additional autoimmune diseases where some have already been tested with CAR T-cells in early research are MS, type 1 diabetes and rheumatoid arthritis. Although this form of immunotherapy is still in the early stages of research in autoimmune diseases, the potential of CAR T-cells to treat these diseases offers hope for more effective and targeted therapies with fewer side effects than current treatments.
Elicera Therapeutics’ CEO comments
BioStock contacted Jamal el-Mosleh, CEO of Elicera Therapeutics, currently Sweden’s only R&D company developing and evaluating CAR T-cell treatments.
Early research shows the potential of CAR T-cells in solid cancer tumours and autoimmune diseases. Even though it is early research – what are your thoughts on the results seen so far?
– It is encouraging to see these new and promising results, although it is too early to draw any concrete conclusions. At Elicera, we work with immuno-oncology only, so the results regarding ovarian cancer are of course very exciting to hear. We have developed a platform technology that has the potential to armour essentially any CAR T-cell therapy to address the greatest challenges in combating solid cancer tumours, and we will be closely following developments in this area.
Why do CAR T-cells seem to have such a broad potential, spanning several major disease areas?
– Our immune system is used to attack micro-organisms and foreign substances, including cancer, which can cause disease and the white blood cells (T-cells) are, in a sense, the main soldiers of the immune system. CAR T-cells have such broad potential across several major disease areas because we can take T-cells from patients and then modify (CAR T-cells) and train them to specifically attack various diseases, such as cancer or as we have recently seen, autoimmune diseases. One “trains” a T-cell to attack a certain disease by inserting a chimeric antigen receptor (CAR) that seeks out a specific target (antigen) on the cell that we want to kill.
– The difficult thing is to identify a target that is expressed on all cells for the disease you want to treat, and not expressed to a greater extent on healthy cells. In solid tumours, this has proven to be particularly challenging, and therefore we have developed a way to arm CAR T-cells (via the iTANK platform) to be able to trigger a parallel immune response, via the patient’s own killer T-cells, against multiple targets on cancer cells.
You have a commercially available platform technology for optimising CAR T-cells – iTANK. Could it be suitable for out-licensing CAR T-cells also for solid tumours if this were to become relevant in the future?
– Absolutely. iTANK is universally combinable with other CAR T-cell therapies, as evidenced by preclinical data that we published in Nature Biomedical Engineering last year. This means that the platform has the potential to arm and improve the effect of all CAR T-cell therapies and hopefully enable the treatment of solid tumours as well. Securing licensing agreements and various types of collaborations for iTANK is a central part of Elicera’s business strategy and therefore we have partnered with a leading life science transactional advisory firm called LifeSci Consulting. While we cannot guarantee that we will complete any transactions, we look forward to evaluating various partnership options with them.
What are your goals for Elicera’s CAR T pipeline for the remainder of 2023?
– An important goal is to start the planned phase I/IIa clinical study that will evaluate Elicera’s CAR T-cell treatment ELC-301 in the treatment of B-cell lymphoma. If the application were to be approved, it would represent a major milestone for both Elicera and Swedish CAR T research. It would not only be the first time that Elicera enters clinical trials with a CAR T-cell therapy, but also the first time our CAR T-cell arming platform, iTANK, will be tested in the clinic.
