“What is cell therapy and what does it have to do with epigenetics?”, one might ask. Well, frankly, you could define cell therapy as treatment with cells. In fact, it is an approach in which cellular material or a biological product proven to have a therapeutic effect is obtained from living cells and then injected or transplanted into a patient [1]. Cell therapy is a common application in immunotherapy, which involves artificially stimulating (training) the immune system to improve its recognition of a particular disease [1].
Chimeric Antigen Receptor T Cell Therapy (CAR-T)
Advances in cancer immunology have accelerated the clinical application of immunotherapy and therefore 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 taking T cells - important white blood cells of the immune system - from blood samples from patients, reprogramming them with the CAR gene and infusing the modified T cells back into the patients [2]. For more information see the image below:
The traditional approach of combining other immunotherapies with CAR-T therapy has been used in recent years. The ultimate goal is to achieve a synergistic effect, which is the interaction between two factors (in this case medications or therapies) with related effects that work together to produce a better result. Nevertheless, existing applications (e.g. CAR-T cells plus immune checkpoint inhibition) showed promising results until most patients failed to derive clinical benefit or developed resistance to such treatment [3,4,5].
The role of epigenetics
It is therefore necessary to think outside the box and include other therapy models in addition to cell therapy in order to maximize the benefit for patients and overcome resistance. This is where epigenetics comes into play! Put simply, epigenetics is the study of the changes that take place on our DNA without changing the genome sequence, but which still influence the expression of our genes.
Epigenetic therapeutics have been used in combination with classical chemotherapies, targeted therapies, other epigenetic agents, and immune checkpoint inhibitors to increase response rates in patients with hematologic cancers and to extend the reach of such treatments to solid tumors. Although in vitro studies usually show synergistic effects when different therapies are combined with epigenetic agents, clinical results tend to show the opposite. In fact, only one combination of chemotherapy and an epigenetic drug has received accelerated approval from the US Food and Drug Administration (FDA) [6]. This treatment includes panobinostat (histone deacetylase inhibitor), bortezomib (proteasome inhibitor), and dexamethasone (glucocorticoid drug).
Over time, promising epigenetic candidates have been identified that have been shown to be synergistic. For example, in 1983, combinations of DNMT-HDAC inhibitors showed promising synergistic effects [7]. However, despite extensive studies, there is no solid evidence for 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 investigated, a current example being EZH2 inhibitors [9].
Much remains to be discovered before a successful combination of epigenetic drugs with cell therapy is possible. Through joint research, MoleQlar Analytics wants to play a pioneering role in the discovery of new epigenetic insights. We hope that these findings will eventually lead to the development of drugs and drug combinations that can be used in precision medicine.
