Mainz chemists and physicians develop nanoparticle-based immunotherapy for cancer
The German Research Foundation (DFG) has established a new Collaborative Research Center on "Nanodimensional polymer therapeutics for tumor therapy" (CRC 1066) at Johannes Gutenberg University Mainz (JGU) and the Max Planck Institute for Polymer Research (MPI-P). Starting in October 2013, the Collaborative Research Center will receive grants totaling approximately EUR 11 million over four years to develop a nanoparticle-based cancer therapy to combat melanoma as an immunogenic tumor model. The Mainz scientists will focus on a form of cancer immunotherapy that is specifically suitable for permanently eliminating minimal residual disease, such as hidden metastases. The new CRC is notable for its interdisciplinary approach: chemists will study the synthetic feasibility and the structure-property relationships of carrier materials, while immunologists and biomedical specialists develop models for the optimal use of such carriers – in the form of a new combination therapy for activating the body’s immune response against the cancer. The coordinator of the new DFG-funded Collaborative Research Center is Professor Rudolf Zentel from the Institute of Organic Chemistry at Johannes Gutenberg University Mainz. Assistant coordinators are Professor Stephan Grabbe from the Department of Dermatology at the Mainz University Medical Center and Professor Katharina Landfester from the Max Planck Institute for Polymer Research in Mainz. In addition, the Board of Directors will include Professor Detlef Schuppan from the Department of Internal Medicine I at the Mainz University Medical Center and Dr. Mathias Barz from the JGU Institute of Organic Chemistry as a representative of young researchers.
The combination of the expertise of Johannes Gutenberg University Mainz and the Max Planck Institute for Polymer Research, one of the leading sites for polymer chemistry in Germany, together with the excellent research structure in the area of tumor immunotherapy at the Mainz University Medical Center, will enable the new CRC to conduct research at the broadest level. "This new Collaborative Research Center will bring together these very strong research areas to create new medical challenges for natural scientists as well as to provide medical research with a stronger natural scientific orientation," said the coordinator of the CRC, Professor Rudolf Zentel. "Researchers from the field of chemistry, alongside immunologists and biomedical specialists, will develop novel, multifunctional, nanodimensional therapeutic agents with the aim of releasing agents and combinations of agents in as cell-specific a way as possible, and to also make it possible to make very sensitive agents, such as RNA, therapeutically usable. In an intensively interdisciplinary process, we will combine innovative therapeutic approaches from immunology and oncology with the synthesis of a broad array of well-characterized, suitably functional polymeric nanoparticles with clear physicochemical characterization in the biological environment."
For the chemists, the challenge is to synthesize well-defined polymeric carrier systems and to modify them, render them functional, and to load them with suitable therapeutic agents. Building on these initial synthetic steps, the scientists will go on to test these carrier systems in cross-sectional projects with respect to their interactions in extracellular media, cellular uptake, and distribution in the body. "Our biomedical specialists will then test these systems in combined tumor immunotherapy based on the targeted induction of inflammation in the tumor, stimulation of the immune response, and neutralization of tumor tolerance," said Professor Stephan Grabbe, Director of the Department of Dermatology at the Mainz University Medical Center.
"This Collaborative Research Center is the fruit of decades of excellent research achievements by Mainz scientists in chemistry and medicine and demonstrates the success of building profiles and specialties in science and research at our university," said the President of Johannes Gutenberg University Mainz, Professor Georg Krausch. Mainz has distinguished itself through its many years of successful activity in the field of polymer research and its current work in CRC 625: From single molecules to nanoscale structured materials, Mainz has become renowned for its great expertise in creating and characterizing the physicochemical nature of nanoparticular systems. This makes it possible to create narrowly distributed functional polymer structures and to investigate their aggregate formation in a biological context. In addition, the new CRC will benefit from extensive expertise in the organic chemistry of natural substances, concentrated in the Center for the Synthesis of Natural Products, which is funded by the federal state of Rhineland-Palatinate, BASF and Boehringer Ingelheim and which contributes to the knowledge of linkers and identification structures as well as a radiopharmaceutical division with outstanding chemical processing options, for example in the field of labeling chemistry and in vivo imaging using PET at the JGU Institute of Nuclear Chemistry. The Max Planck Institute for Polymer Research is also a competent partner for the synthesis and characterization of polymeric carriers.
The Mainz University Medical Center has established a specialty area in immunology with experience in immunotherapy as well as a Center for Translational Oncology (TRON) in combination with new spin-off firms, such as GANYMED, which can supply anti-tumor antibodies. Overall, there is a longstanding tradition of basic research in tumor immunology at the Mainz University Medical Center with the development of new concepts in tumor immunotherapy, culminating in clinical trials focused on melanoma, for example, in Collaborative Research Center 432, which concentrates on tumor immunology and experimental therapy. In addition, the Center for Natural Sciences and Medicine, headed by Professor Stephan Grabbe, has encouraged similar kinds of collaboration between medicine and the natural sciences at Johannes Gutenberg University Mainz for more than 30 years.
"The new Collaborative Research Center shows that it makes sense to encourage the development of strong network structures in Mainz and the region. The concept of the CRC is promising because initial successes, specifically in melanoma treatment, have demonstrated that this treatment concept may contribute to making it possible in the future to successfully treat cancers that are now incurable," emphasized Professor Förstermann, Chief Scientific Officer of the Mainz University Medical Center.