CAR-T cell therapy is a new type of cancer immunotherapy that uses the patient’s own T cells to fight certain types of cancer. In order to do this, the cells are extracted in the clinic by leukapheresis and then genetically reprogrammed in vitro in such a way that they can use a chimeric antigen receptor (CAR) to recognize cancer cells and other cells that have a special antigen on their surface. Following lymphodepleting chemotherapy, the reprogrammed cells are administered to the patient though an infusion. They then proliferate and can trigger the immune response.
In August 2017, the first CAR-T cell therapy became available in the USA in the form of Kymriah® (CTL019 / tisagenlecleucel). Kymriah® was granted FDA approval for children and young adults aged up to 25 years old diagnosed with acute lymphocytic B-cell leukemia (ALL) who are not responding to the usual therapies or have already suffered relapses. In May 2018, approval was also granted for adult patients with diffuse large B-cell lymphoma (DLBCL) who had suffered relapses after two or more lines of systemic therapy or who have not responded to therapy at all. On August 27, 2018, Novartis announced that it had received approval from the European Commission for both these indications.
Fraunhofer IZI has long since been a key manufacturing and development site for this innovative CAR-T cell therapy for various clinical trials throughout Europe. Over the next few years, prescription-only, approved T-cell therapies will also be manufactured on an interim basis in the Main Department of GMP Cell and Gene Therapy at Fraunhofer IZI, alongside investigational medicinal products. Following a one-year technology transfer period from Novartis’ Morris Plains site in New Jersey, USA, and after obtaining manufacturing authorization in accordance with Section 13 of the German Medicinal Products Act (AMG), the first clinical batch was manufactured at Fraunhofer IZI in Leipzig in August 2016. The Main Department of GMP Cell and Gene Therapy has continuously produced CAR-T cell therapies for Novartis ever since.
Until the end of 2018, batches in the high double-digit range were delivered to patients, including many children, all across Europe. The extremely complex process involved in manufacturing a cell preparation takes several days and involves not only state-of-the-art instrument engineering, but also manual tasks. Before being cleared for human use, extensive analytical release tests are first conducted on the finished product (e.g. concerning identity, purity, in vitro efficacy, microbiological safety) and the batch documentation is reviewed in detail.