SFB 643:  Strategies of Cellular Immune Intervention

Final Report Abstract

Immunological mechanisms play a pivotal role in numerous human diseases. The overall goal of our Collaborative Research Centre CRC 643 was the stepwise translation of basic immunologic findings into novel therapies based on manipulating the immune system. Our vision was to develop such novel immune intervention strategies to either stimulate insufficient immunity (as required to fight cancer or infections) or dampen undesirable immune responses (as in autoimmunity, allergy, and graft rejection). After twelve years of funding several novel targets and new immune intervention strategies have indeed been identified, and we are testing three of them already in the clinic. Advanced and universally applicable third generation "designer" dendritic cell (DC) based vaccines are used to induce enhanced immunity to cancer or infections. The adoptive transfer of virus-specific T cells or B cells is currently explored in clinical trials to fight virus infections which frequently occur after allogeneic stem cell transplantation and are still a major clinical problem. Besides these cellular therapies, two recombinant molecules have been developed to a stage allowing clinical testing in the near future, namely a dual-specificity antibody designed to attack leukemia cells optimally, and the so-called soluble CD83 molecule which can modulate immune reactions such as the ones causing rejection of allografts or autoimmunity. Members of the CRC also identified several new targets which will finally help to diagnose or treat common human diseases much better. Groundbreaking new basic immunology findings, e.g. that sodium ions not only regulate blood pressure but also regulate immune cells, have also been made and will find their way into textbooks and finally into clinical medicine.

Completed projects