In recent years, a new class of immunotherapy has emerged: CAR T cells. This treatment was primarily developed to treat cancer. The treatment works by genetically modifying T cells, a type of immune cell, to produce a chimeric antigen receptor (CAR) on their surface, which enables them to recognize and attack cancer cells. There are currently six FDA-approved CAR T cell therapies, all of which target different types of blood cancer. In addition, several hundred CAR T cell therapies are being developed globally by biotechnology companies.
However, the development of CAR T-cell therapy has not been without challenges, primarily due to the high rate of relapse and the serious side effects experienced by many patients. Furthermore, no CAR T-cell therapy has yet been approved for the treatment of solid tumors.
Read more about CAR T-cell therapy here.
Shown effect on ovarian cancer in mice
There are two main challenges that CAR T-cell therapies face in the treatment of solid tumors. The first is the heterogeneous expression of CAR target antigens, which increases the risk that some tumor cells escape attack and instead form CAR T-cell-resistant tumors. The second challenge is local immunosuppression, which makes it more difficult for T cells to infiltrate the tumor and also inhibits their potential to kill cancer cells.
In February, a study was published in The Journal for ImmunoTherapy of Cancer by researchers from Karolinska Institutet which showed that CAR T-cell treatment showed efficacy in mice with ovarian cancer, a solid tumor.
The study chose to focus on the mesothelin protein, which is found on many ovarian tumors. The researchers tested three types of CAR molecules programmed to attack that particular protein. All three CAR-T cells significantly extended the lives of mice with cancer, compared to those in the control group. But one of the three CAR-T types, called M1xx CAR-T cells, had a superior effect. The mice injected with that molecule shrank their tumors and lived even longer than the others. Several of the mice were even cured.
Potential in autoimmune diseases
The potential of CAR T-cell therapy does not seem to stop at cancer. This form 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 provide broad suppression of the immune system, which can lead to an increased risk of infections and other side effects. Researchers believe that CAR T cells could become highly relevant for treating autoimmune diseases through a more targeted approach. Researchers are currently 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, and the treatment was well tolerated, with the most serious side effect being mild cytokine release syndrome.
Additional autoimmune diseases where some have already been tested with CAR T cells in early research include 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 got in touch with Jamal el-Mosleh, CEO of Elicera Therapeutics, Sweden's currently only R&D company which develops and evaluates CAR T-cell therapies.
Early research shows the potential of CAR T cells in solid cancers and autoimmune diseases. Although this 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 exclusively with immuno-oncology, so the results around ovarian cancer are of course very exciting to hear. We have developed a platform technology that has the potential to arm virtually all CAR T-cell therapies to meet the biggest challenges of fighting solid cancer tumors and we will follow developments in this area closely.
Why do CAR T cells seem to have such broad potential, spanning several major disease areas?
– Our immune system is used to attack microorganisms and foreign substances, including cancer, that can cause diseases and the white blood cells (T cells) can be said to be the main soldiers of the immune system in a way. 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 different diseases, such as cancer or as we have recently seen, autoimmune diseases.
– You “train” 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 you want to kill. The difficulty is to identify a target that is expressed on all cells for the disease you want to treat and that is not expressed to a greater extent on healthy cells. In solid tumors, 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 optimizing CAR T cells – iTANK. Could it be suitable for out-licensing CAR T cells also for solid tumors if this were to become relevant in the future?
– Absolutely. iTANK is universally combinable with other CAR T-cell therapies, as supported by preclinical data we published in Nature Biomedical Engineering last year. This means that the platform has the potential to arm and enhance the efficacy of all CAR T-cell therapies and hopefully enable the treatment of solid tumors 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 entered into a collaboration with a leading life science transaction advisory firm called LifeSci Consulting. While we cannot guarantee that we will complete any transactions, we look forward to evaluating various options for partnerships with them.
What goals do you have for Elicera's CAR T pipeline for the rest of 2023?
– An important goal is to begin the planned Phase I/IIa clinical study that will evaluate Elicera's CAR T-cell therapy ELC-301 in the treatment of B-cell lymphoma. If the application is approved, it would represent a major milestone for both Elicera and Swedish CAR T research. It would not only be the first time Elicera enters clinical trials with a CAR T-cell therapy, but also the first time that our platform for weaponizing CAR T cells, iTANK, will be tested in the clinic.