PRIAT · Profiling Responders In Antibody Therapies

Therapeutic antibodies are the largest and fastest growing class of pharmaceutical biotechnology products, with annual sales above 30 billion US$. In some cases, antibody products have revolutionized the management of patients, e.g. TNF-blocking antibodies in Arthritis or Rituxan in lymphoma. However, for most antibody therapies, only a subset of patients benefit from treatment. Thus, there is an urgent need to develop more potent therapeutic antibodies and to understand the molecular basis for the differential responses of patients to treatment.This consortium consists of European centres of excellence being pioneers in the field of therapeutic antibody development and (pre-) clinical studies and will tackle both of these challenges:Innovative immunocytokines L19-IL2 and F8-IL10 are developed by Philogen for the treatment of metastatic melanoma and rheumatoid arthritis respectively at multiple clinical centres including Graz and Tübingen.Building on the strong background in proteomics biomarker discovery of ETH Zurich and Philochem, an innovative methodology (“HLA-peptidome analysis”) will be utilized for gaining information on the immune response in animal models and patients which receive antibody treatments. This method is based on the observation that HLA molecules in complex with peptides can be detected in the patient blood and that hundreds of HLA-associated peptides can be sequenced by mass spectrometry. The technology will be used for the profiling of responses following antibody treatment for patients with cancer and rheumatoid arthritis, as well as animal models of transplant rejection. This systems biology approach has the potential to revolutionize patient stratification in very short time.Finally, patient selection strategies will be investigated using the clinical-grade immunocytokine (F8-IL10) as an example, monitoring antibody uptake at the site of disease by immuno-PET imaging methodologies at VUMC Amsterdam in collaboration with Philogen.""