“Cancer immunotherapy using oncolytic viruses and CAR T-cells”
Prof. Magnus Essand, Gene, cell and immunotherapy of cancer, Rudbeck laboratory, Uppsala University
Immunotherapy of cancer has emerged as one of the most promising new developments in medicine. This is mainly due to the introduction of immune checkpoint inhibitors (anti-CTLA4, anti-PD1 and anti-PDL1 antibodies), which kill cancer cells through activation of anti-tumor cytotoxic T lymphocytes (CTLs). Their action has demonstrated that the balance between immune activity and immune suppression in cancer tissues is a key determinant of success. Pre-existence of CTLs recognizing tumor-specific antigens in cancer cells is required to achieve a good response. If anti-tumor CTLs are not pre-existing, but an antigen that could be recognized by anti-tumor CTLs has been identified, T-cells isolated from peripheral blood of cancer patients can be genetically engineered with a new receptor targeting that antigen. Upon adoptive transfer back to the patient, the engineered T-cells specifically recognize and kill cancer cells presenting the target antigen. This has led to the development of chimeric antigen receptor (CAR) T-cell therapies, which works notably well for leukemia and lymphoma. A third form of immunotherapy on the verge of breakthrough is oncolytic viruses, which selectively lyse cancer cells, induce immunogenic cell death and thereby deceive the immune system to believe that the tumor is foreign and needs to be eradicated. The lecture will present ongoing clinical studies with oncolytic viruses and CAR T-cells and the development of next generation viruses and T-cells.
Magnus Essand obtained his PhD in Uppsala, Sweden in 1995 and then received four years of postdoctoral training with Ira Pastan at the National Cancer Institute in Bethesda, Maryland. He returned to Sweden in 2000 to start up his own research group and became Professor at the Department of Immunology, Genetics and Pathology at Uppsala University in 2009. Essand has published seventy original peer-reviewed scientific articles and eleven peer-reviewed overview articles. He has tutored ten PhDs to completion of their PhD theses and is currently the main supervisor of three PhD students and four postdocs. Essand is a scientific reviewer for many international journals and funding agencies.
The research in Essand’s group mainly concerns development and advancements of translational cancer immunotherapies, with the focus on oncolytic viruses, chimeric antigen receptor (CAR) T-cells and dendritic cell-based vaccines. Most of the work is preclinical and based on mouse
models but two oncolytic viruses developed in Essand’s laboratory are now being evaluated in clinical phase I trials for neuroendocrine cancer and prostate cancer. Essand is also involved in a CAR T-cell trial for lymphoma and leukemia patients and a new CAR T-cell expansion protocol developed in his laboratory is about to be evaluated in an upcoming clinical trial.