Periodic Reporting for period 1 - Tumor-Treg-Targeting (Training Network for the education of the next generation scientist in targeting the supressive capacity of regulatory T-cells specifically within tumours) Reporting period: 2018-06-01 to 2020-05-31 Summary of the context and overall objectives of the project Tumour-Treg-Targeting is a collaborative research and training project established to provide innovative and comprehensive training in antibody-based drug design to next-generation scientists in academia and industry in order to enable them to develop the next generation of antibody-based biologicals targeting and shifting the immunological environment specifically within tumours. These next-generation antibodies will be designed to exploit all the potential of the immune system to fight cancer. The project will address the following main goals:Objective 1: to develop novel biologicals that can target cell populations - such as cancerous cells or specific subtypes of leukocytes - with unprecedented specificity.Objective 2: to specifically engage particular cell types of the innate immune system within tumours with applied biologicals in a directed fashion.Objective 3: to target known immune-modulating cytokines or known check-point inhibitors directly into established tumours. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far All students have been enrolled in PhD programs and in the different educational activities of the network. In parallel, the experimental work progress in fulfilling the different aims of the project. The internships of the students in the Aduro facilities, the industrial partner of this project, was instrumental in advancing in each student’s experimental program. The work performed in the network has already achieved results that were published in peer-reviewed journals:1) A novel efficient bispecific antibody format, combining a conventional antigen-binding fragment with a single domain antibody, avoids potential heavy-light chain mis-pairing. Huang S, Segués A, Hulsik DL, Zaiss DM, Sijts AJAM, van Duijnhoven SMJ, van Elsas A. J Immunol Methods. 2020 Aug;483:112811. doi: 10.1016/j.jim.2020.112811. Epub 2020 Jun 19.2) Bispecific antibodies targeting dual tumor-associated antigens in cancer therapy. Huang S, van Duijnhoven SMJ, Sijts AJAM, van Elsas A. J Cancer Res Clin Oncol. 2020 Dec;146(12):3111-3122. doi: 10.1007/s00432-020-03404-6. Epub 2020 Sep 28.3) Isotype selection for antibody-based cancer therapy. Vukovic N, van Elsas A, Verbeek JS, Zaiss DMW. Clin Exp Immunol. 2021 Mar;203(3):351-365. doi: 10.1111/cei.13545. Epub 2020 Nov 30.4) Purification of murine immunoglobulin E (IgE) by thiophilic interaction chromatography (TIC). Vukovic N, Harraou S, van Duijnhoven SMJ, Zaiss DM, van Elsas A. J Immunol Methods. 2021 Feb;489:112914. doi: 10.1016/j.jim.2020.112914. Epub 2020 Nov 14. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) The different experimental projects continue to characterize further the properties of the novel therapeutic molecules developed within the network. It is expected that novel technologies will be developed, and their potential in preclinical cancer models will be demonstrated.