German Cancer Research Center, Division of Cellular Immunology, Im Neuenheimer Feld 280, Heidelberg

Activation of naïve CD8 T cells for clonal expansion and development of effector and memory function requires three signals: i) TCR mediated signal 1, ii) CD28 mediated signal 2 and iii) cytokine receptor mediated signal 3. Signal 3, which can be delivered from dendritic cell released IL-12 or IFNais able to prevent induction of tolerance. Human tumor cell modification by infection with the avian paramyxovirus Newcastle Disease Virus (NDV) is an efficient and safe way to produce the autologouscancer vaccine ATV-NDV with pleiotropic immune stimulatory properties providing signal 2 and 3. Tumor cell surface expressed viral haemagglutinin-neuraminidase (HN) and the cytoplasmic viral double stranded RNA (dsRNA) activate cells of the innate immune system, including plasmacytoid dendritic cells to produce high amounts of IFN-a. Major findings of clinical phase II studies with ATV-NDV vaccine which were performed in cooperation with clinical colleagues in Germany since 1990 will be summarized. They include a total number of 382 patients. 

The maintenance of long-term polyclonal antitumor memory is considered of utmost importance for improvement of long-term survival of cancer patients. We will discuss our strategies of maintaining and augmenting such antitumor memory in cancer patients by active anti-tumor vaccination or by adoptive memory cell transfer. New bispecific T cell stimulatory molecules were produced in recent years which further improve the effectivity of our strategies.