Project Title: Programming of breast cancer microenvironment to create a ”hot” immune-responsiveness in cancer

Project No: lzp-2021/1-0283

Period: 1 January 2022 – 31 December 2024

Project costs: 299999,70 EUR

Principle Investigator: Dr.biol. Anna Zajakina

Collaboration: Latvian Institute of Organic Synthesis

Summary

Immunosuppressive tumour microenvironment is the main bottleneck causing low patient response in cancer immunotherapy. In breast cancer and other solid tumours, tumour-associated macrophages (TAM) represent a key immune regulatory component, which supports cancer progression. The phenotypic plasticity of TAM made these cells an ideal target for cancer treatment. Nevertheless, how the macrophages are programmed within the tumour remains unknown, moreover, many hypotheses of TAM polarization are insufficiently proved and currently represent unsubstantiated speculations. The aim of this proposal is to develop a new  3D heterotypic cell culture model for investigation of targeted TAM programming, and to approve anti-cancer properties of the reprogrammed TAMs in preclinical models. The project will allow identification the key factors (secretome) determining TAM polarization and regulating their cross-talk with cancer cells. To convert tumour to the immunologically “hot” state, we will apply alphaviral vectors, producing reprogramming cytokines/chemokines in combination with theranostic effector compounds, for activation of TAM anti-cancer properties in a 3D environment and in orthotopic murine model. The project results will facilitate the development of a new immunotherapy platform based on targeted programming of the key components of tumour microenvironment with powerful virus gene delivery vectors and multifunctional compounds.

Information published 03.01.2022.