Immunotherapy

The Immunotherapy Development Center (IDC) of TRON focusses its research on improving immunotherapy. Immunotherapy exploits the natural components of our body’s immune system, which we modulate and redirect for treatment of cancers, infectious diseases and/or auto-immune disorders.

To this aim, we follow different approaches ranging from therapeutic or prophylactic vaccines to nanoparticle-based drug delivery.

Vaccines have served for centuries to immunize people against infectious diseases. These so-called prophylactic vaccines are applied before the infection. They induce an immune response against pathogenic viruses or bacteria to prevent infection, severe illness or death. A challenge in the fight against infectious diseases is the rapid evolution of viruses, which requires rapid vaccine development or adjustment. At TRON we develop RNA-based vaccines that will enable us to react flexibly and quickly to mutating or newly appearing viruses.

In our fight against cancer, in contrast, we need vaccines that can be applied and act after tumors have developed in patients. Such vaccines should cure cancers and are therefore called therapeutic vaccines. An enormous challenge to cancer vaccines is the great variability of mutations that cause tumors in individual patients. At TRON we have the expertise to look onto patient-specific tumor mutations. We sequence the genome and the mRNA expressed in cancer cells to find the individual signatures (neoantigens) in order to create specific vaccines using our flexible RNA vaccine vectors. We have already several clinical evidences that this approach constitutes the novel and successful mRNA based immunotherapy against cancers.

In addition recently, our pre-clinical studies have demonstrated that vaccines can cure autoimmune diseases, such as encephalomyelitis in mice, which is the experimental model of multiple sclerosis in human.

Cellular therapies rely on engineered immune cells (mainly T cells) that specifically attack and eradicate tumors. Cellular therapies have become a successful clinical translation of innovative research approaches for treatments of cancer patients. We and other investigators worldwide have obtained highly promising results perfoming adoptive transfer of tumor-specific lymphocytes. Here, immune cells, especially cytotoxic T cells, are genetically engineered in culture to express cancer-reactive effector molecules – such as chimeric antigen or T cell receptors (CAR or TCR) – and infused back into patients. The next step in this technology that we also pursue at TRON is to engineer the immune cell directly in the patient body. Further, we aim to improve the anti-cancer activity of the cells.

We believe that combination of drugs, rather than single treatments, will unlock the full potential of immunotherapy. Although single agent therapies may be effective, the outgrowth of tumors that have become resistant to a treatment remains a challenge. Different therapies exploit different components and mechanisms of the immune system, and some tumor cells find specific ways to escape the treatments. Combining immunotherapies promises to suppress escaping tumors much more effectively by closing several doors for tumors to escape at the same time.

At TRON we explore the combined effects of RNA vaccines with radiotherapy or chemotherapy and antibody therapy. We provide comprehensive pre-clinical data that pave the way for clinical testing of promising novel combination therapies.

Nanoparticles are drug delivery agents, which protects the cargo by degradation, while preserving the targeting of organs and cells in the body upon different route of delivery. These particles are very small molecular carriers, far below 1 µm in diameter. Among those the liposomes are the most widely known nanoparticles.

At TRON, we use nanoparticle formulations to deliver highly divers drug formats, ranging from small molecules to nucleic acids such a microRNA, mRNA or DNA. The great variety of different nanoparticles allows us to define and choose the best formulation for our vaccines and drugs to cure specific diseases.

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