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General information / Summary
Hans-Georg Rammensee
Julia-Stefanie Frick
Cécile Gouttefangeas
Thilo Stehle
Stevan Stevanović
Tobias Feuchtinger
Rupert Handgretinger
Martin Röcken
Arnulf Stenzl
Dominik Hartl

Bodies of the Collaborative Research Center

 

Coordinator:

Prof. Dr. rer. nat. Hans-Georg Rammensee

Vice Coordinators:

Prof. Dr. med. Julia-Stefanie Frick
Dr. rer. nat. Cécile Gouttefangeas
Prof. Dr. rer. nat. Thilo Stehle

Scientific Secretary:

Prof. Dr. rer. nat. Stefan Stevanović


Executive Board:

Prof. Dr. rer. nat. Hans-Georg Rammensee
PD Dr. med. Tobias Feuchtinger
Prof. Dr. med. Julia-Stefanie Frick
Dr. rer. nat. Cécile Gouttefangeas
Prof. Dr. med. Rupert Handgretinger
Prof. Dr. med. Martin Röcken
Prof. Dr. rer. nat. Thilo Stehle
Prof. Dr. med. Arnulf Stenzl
Prof. Dr. rer. nat. Stefan Stevanović

Integrated Research Training Group: 

Coordinators:

Prof. Dr. med. Dominik Hartl
Prof. Dr. med. Julia-Stefanie Frick

 

 

Summary


CRC 685, “Immunotherapy“, started its existence in July 2005, with a particular focus on immunotherapy of cancer. At that time, passive immunotherapy with monoclonal antibodies was well established in clinical practice. Active immunotherapy of cancer, however, was not considered a plausible therapeutic avenue by many of those involved in clinical cancer therapy and cancer biology research. This attitude has since changed considerably, and we are proud to be able to say that our CRC, and also its predecessors CRC 120 and 510, substantially contributed to this positive development. In the meantime, the first active immunotherapies have been approved by the FDA, and several clinical phase II studies now indicate an impressive clinical benefit awarded by an active specific immunotherapy approach targeting several antigens simultaneously. The most advanced study of this kind, a multipeptide “IMA901” vaccination in renal cell carcinoma performed under participation of CRC 685 members, reported impressive overall survival benefit correlating with good immune responses (Walter et al., Nat Med, July 2012). Thus, a first generation of active immunotherapy of cancer is well underway. The pivotal aim of our CRC 685 in the third (and final) 4-year-term (until 2017) is now to prepare the ground for the “next generation” of immunotherapy. We anticipate, on the one hand, that even more efficient immune responses against cancer could be elicited by targeting tumor specific mutations on an individualized basis. On the other hand, we are aiming for an immunotherapy with broad peptide cocktails representing overexpressed (not mutated) peptides to cover all patients, independently of HLA typing. Such a cocktail could be used immediately after surgery, and could be supplemented later by individualized peptides. Pursuing both options, i.e. identifying the relevant antigens for both approaches – overexpressed and mutated – is well covered by the CRC 685 projects for the next term, using technologically advanced equipment acquired very recently. Here, the CRC took advantage of the activities of the Opens external link in new windowGerman Consortium for Translational Cancer Research (DKTK). This consortium will also be helpful in the implementation and financing of clinical phase I/II studies based on the findings that emerge from our CRC. The performance of clinical studies that are based on the discoveries made by our CRC has only recently been made possible: the new GMP center on our campus was certified for the production of GMP grade peptides as active pharmaceutical ingredients on March 7, 2012. In addition, and most important for an advanced and more efficacious immunotherapy, we will pay particular attention to immune response players and modifiers in general in order to be able to positively influence the response to our selected cancer antigens in vaccinated patients. For this purpose, we intend to cover broad aspects of immune regulation, in particular involving Innate Immunity, signal transduction, immune senescence, and inflammation. Since immune responses that are desirable in cancer and infection can be detrimental in autoimmunity, or vice versa, it is vital to investigate and gain an understanding about the governing factors by analyzing the immune responses in these three conditions. On top of these basic research activities, we plan to increase, for very practical reasons, our efforts in bioinformatics and in immunomonitoring.

A key objective of our CRC is to amass a solid and excellent foundation of knowledge on the immune system in order to use this for the benefit of patients, in particular those suffering from cancer. It is now generally accepted that the immune system can indeed actively fight cancer; thus, Paul Ehrlich’s foresight has been confirmed. Several factors contribute to bringing about efficient anti-cancer immune responses: i) innate immune activation is now appreciated as a critical factor for the activation of sufficient anti-tumor responses. ii) antibodies are able to recognize cell surface molecules on cancer cells and either block their function, as is the case for antibodies against growth factor receptors, or activate cellular or complement mediated cytotoxicity. Therapeutic antibodies are now well established in clinical application and, with the participation of our latest spin-off, Synimmune, a new generation of more efficient antibody formats is being developed. iii) T cells provide a vast repertoire for individualized immunotherapy. In contrast to the limited repertoire of antibody specificities suitable for immunotherapy of cancer, T cells are able to target a very broad range of structures, since all cancer-related changes inside a cell can, in principle, be recognized as HLA-presented peptides on the cell surface. Accordingly, our overall aim remains that of identifying suitable antigens for immunotherapy and investigating all important aspects necessary for achieving an effective immune response in the patient. These aspects include mechanisms of Innate Immunity, immune regulation, signaling in immune cells, and cellular interactions in general. Thus, the study of these areas requires a broad and excellent research basis. In the previous funding phase of CRC 685 this basis was expanded considerably, providing the ideal setting for the ambitious course set for the final phase. 

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