Cancer is a common disease causing significant impact in every nation via mortality and morbidity. Worldwide, more than 14 million new cases of cancer are diagnosed every year and over 8 million people die from cancer yearly. The most common types of cancer are lung cancer, female breast cancer, bowel and prostate cancers. The lifetime risk of developing cancer is ~42% for males and ~38% for females.
A great proportion of these cancers are ill- or not treatable by standard treatment options. Adoptive cell transfer (ACT), is often referred to as the next generation cancer therapy and its success in various trials has been impressive. Recently, on 30.08.2017, Kymriah (tisagenlecleucel) was approved by the FDA for certain groups of patients with a form of acute lymphoblastic leukemia (ALL). This is the first in history approval of a CAR-T cell therapy. Subsequently, on 18.10.2017, Yescarta (axicabtagene ciloleucel), also a CAR-T cell therapy, was FDA approved for patients with certain types of large B-cell lymphoma. To date most successful clinical trials have targeted hematological malignancies and treatment of solid tumors by this approach has been challenging for many reasons.
Our goal is to use our bench experience to define the major criteria that must be met to create a reliable, safe, and effective platform for adoptive T cell therapy. We want to utilize this platform to create therapy that can be deployed against a broad range of tumors, solid as well as hematological. The major goals of any immunotherapy is to combine a specific therapy with minimal toxic side effects in addition to the establishment of a durable clinical response and an immune memory in advanced cancers. We study not only CAR-T cells, but also TCR based adoptive therapy and dendritic cell vaccine therapies. Many projects are still at early stages, but some are entering clinical trials.
Our current clinical focus is on two tumor-targeting TCRs that were isolated from long-term survivors after cancer vaccination (Adoptive T-Cell therapy). The longevity of the TCRs in these patients without side effects makes them especially suitable for clinical trials. The two tumor antigens we are targeting are the universal antigen telomerase and the public neoantigen derived from TGFβRII frameshift mutant. Telomerase is very important in oncogenesis and 80-90% of all cancer cells have reactivation or up-regulation of telomerase. TGFβRII mutations are common in colorectal, gastric, pancreatic, biliary tract, lung and brain cancers. Clinical trials for both targets are underway. We have other potential candidate targets in the pipeline and we will be mentioning those here later as our work progresses.