"What is cell therapy and what does it have to do with epigenetics?", you could ask yourself. Well, openly, one could define cell therapy as treatment with cells. In fact, it is an approach in which cellular material or a biological product that has been proven to have a therapeutic effect is obtained from living cells and then injected or transplanted to a patient [1]. Cell therapy is a common application in immunotherapy, which is about artificially stimulating the immune system in order to improve its detection of a certain disease [1].
Chimera antigen-receptor-t cell therapy (car-t)
The progress in cancer immunology has accelerated clinical use of immunotherapy and thus also cell therapy. Therefore, cell therapy is mainly used in cancer treatment. One of the most effective treatments is Chimeric Antigen Receptor T-Cell Therapy (Car-T) [2]. In short, Car-T is based on the principle of removing T cells-important white blood cells of the immune system-from blood samples from patients, reprogramming them with car gene and infusing the changed T cells again [2]. For more information, see illustration below:
The traditional approach to combine other immunotherapies with Car-T therapy has been used in recent years. The ultimate goal is to achieve a synergistic effect, i.e. the interaction between two factors (in this case medication or therapies) with related effects that work together to achieve a better result. Nevertheless, existing applications (e.g. car-t cells plus immune checkpoint inhibition) showed promising results until most patients did not draw clinical benefits from it or developed resistance to such treatment [3,4,5].
The role of epigenetics
Therefore, you have to look outside the box and, in addition to cell therapy, also include other therapy models in order to maximize the benefits for the patient and overcome resistance. At this point, epigenetics comes into play! To put it simply, epigenetics is the teaching of the changes that take place on our DNA without changing the genom sequence, but which still influence the expression of our genes.
Epigenetic therapeutic agents were used in combination with classic chemotherapy, targeted therapies, other epigenetic agents and immune-checkpoint inhibitors to increase the response rates in patients with hematological cancer and to expand the reach of such treatments to solid tumors. Although in vitro studies usually show synergy effects when different therapies are combined with epigenetic agents, the clinical results rather show the opposite. In fact, only a combination of chemotherapy and an epigenetic drug has received an accelerated approval from the American Food and Drug Administration (FDA) [6]. This treatment includes Panobinostat (Histon Deacetylase Inhibitor), Bortezomib (Proteasom inhibitor) and dexamethasone (glucocorticoid drug).
Over time, promising epigenetic candidates have been identified who have proven to be synergistically. In 1983, for example, combinations of DNMT HDAC inhibitors showed promising synergy effects [7]. Despite extensive studies, however, there is no valid evidence of the effectiveness of epigenetic drugs, e.g. B. in the treatment of acute myeloid leukemia (aml) [8]. Numerous combinations with immune checkpoint inhibitors are currently being examined, a current example are EZH2 inhibitors [9].
A lot has to be discovered until a successful combination of epigenetic drugs with cell therapy. Through joint research, Moleqlar Analytics wants to play a pioneering role in the discovery of new epigenetic knowledge. We hope that these findings will eventually lead to the development of active ingredients and combinations of active ingredients that can be used in precision medicine.
