Research in tumor immunology and molecular oncology
Cancer Vaccine Trials
Recent progress in human cancer immunology has facilitated the identification of potentially immunogenic antigens that can be used to activate the patients' immune system to specifically recognize and destroy tumor cells. In turn, the detailed knowledge of T cell-defined tumor antigens has opened the possibility to design therapeutic cancer vaccines. In particular the Ludwig Institute for Cancer Research and its affiliates have initiated a large number of clinical trials using peptides, proteins or antigenic constructs derived from tumor-associated antigens, administered either alone or with adjuvans. Our clinical program is focused on the evaluation of different routes and schedules of immunization, and the role of adjuvans and viral constructs for the induction of specific immune responses against cancer cells. Importantly, newly identified T cell epitopes are evaluated for clinical application. Our clinical vaccine trials are designed to treat patients with all tumor entities that are positive for individual antigens.
Novel immunotherapeutic approaches have generated the need for monitoring the magnitude and functional potential of post-vaccination T cell responses. The methods currently used in vivo and in vitro include (i) the chromium release assay to assess CTL function, (ii) the detection of cytokine-secreting T cells (e.g. ELISPOT, cytospot assays), (iii) PCR-based analysis of the TCR repertoire (immunoscope), and (iv) soluble fluorescent peptide/MHC class I multimeric complexes ('tetramers'). In particular, the latter approach allows direct visualization of antigen-specific T cells in homogeneous, unmanipulated populations and represents a very potent and sensitive monitoring tool. Importantly multimer staining can be combined with other techniques, such as phenotypic markers, single cell cytokine release assays, and immunoscope for further characterization of antigen-specific T cells.
Serological analysis of recombinant tumor cDNA expression libraries (SEREX) introduced by Michael Pfreundschuh and collegues in 1995 identifies tumor antigens based on humoral immune responses in cancer patients. For this purpose cDNA expression libraries are immunoscreened with autologous sera from cancer patients. Until now, the technique has identified more than 2000 tumor antigens in various tumor types as detailed in the SEREX database. So far, SEREX was successful in the identification and characterization of several important tumor antigens that are being evaluated in active immunotherapy protocols.
Laboratory of Molecular Oncology
The Laboratory of Molecular Oncology was inaugurated in 1977 thanks to the generous support of the Julius Müller Stiftung für Krebsforschung aiming to provide space for applied cancer research within the Department of Oncology.
Initiated by a large private donation, the Stiftung für Angewandte Krebsforschung was founded in 1982 and has continued since to be a major source of support, allowing for innovation and continuity.