The conventional cytotoxic chemotherapy has certainly earned its keep in the treatment of tumor diseases. The absolute use of such a therapy is however highly dependent on the individual tumor biology. In today’s clinical practice, such therapies are however usually unspecific. This, especially in combination with the commonly severe side effects of the cytotoxics, leads to frustration in the patients. New targeted therapies and different immunotherapies have the potential to supersede conventional chemotherapies. A deeper understanding of tumor genetics and immune regulatory pathways, the signaling cascades which serve to circumvent the immunosurveillance of the tumor in particular, have led to the renaissance of tumor immunotherapy.
Checkpoint inhibitors, for instance drugs such as nivolumab (anti-PDL1-antibodies), block one of the emergency exits used by the tumor against successful immune defense. Nivolumab is the first PD-1 inhibitor that demonstrated better survival rates than docetaxel in comparative studies of patients with non small cell lung cancer. Impressive results of this form of immunotherapy have also been reported for malignant melanoma. The scientific and clinical focus of the NextGen Oncology Group is the development and use of cancer vaccines on the basis of mutated neoantigenes. The aim is the production of individually specific peptide vaccines. For the development of the vaccine, all of a tumor’s genes that code protein are examined for mutations (exome sequencing). All genetic mutations found in the tumor are then matched to an exome sequencing that has been simultaneously carried out on the blood. This leads to the identification of genetic markers that are absolutely specific to the tumor and thus highly useful in developing a personalized vaccine. In a further step, we assess whether and if so, which part of the patient’s mutation-carrying section of protein of the individual antigen-presenting system (HLA-Haplotype) can be shown to the immune cells.
Exactly this section will then be rebuilt and used as a vaccine. A personalized cancer vaccine usually contains a group of up to ten of such absolutely specific peptides.
The main steps of our vaccine development process and vaccine application are illustrated in the Figure below.