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H2020Doctoral network2021–2025

CAPSTONE · Training experts in antigen processing to deliver new drug prototypes for cancer and autoimmune diseases

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2021-01-01 → 2025-06-30
EU contribution
€3,968,731
Participants
10
Scheme
MSCA-ITN

Lines connect the coordinator with its partners.

Results in brief

Training experts in antigen processing to deliver new drug prototypes for cancer and autoimmune diseases

Cancer is still one of the leading causes of death in Europe despite the development of targeted therapies. Cancer immunotherapy has proven to be a new, effective strategy, but it is only effective in a fraction of patients. Modulation of the immune system is also the basis of the treatment of autoimmune diseases. These highly prevalent and complex diseases are increasing at an alarming rate across Europe. Small-molecule personalised treatments have the potential for tailor-made immune-oncology and to replace conventional unsatisfactory immunosuppressant approaches. Current trends in immunotherapy are to develop immuno-modulatory small molecules for intracellular targets for single therapy or combination with existing treatments. CAPSTONE scientists have recently identified the key pathway of intracellular antigen processing for modulating the immune response. ERAP/IRAP enzymes that generate antigenic peptides have thus emerged as promising targets for cancer immunotherapy and autoimmune disease treatments. The main research objective of CAPSTONE was to deliver disruptive therapeutic innovation in two areas – autoimmune diseases and cancer, and, in particular, to - Obtain a mechanistic and quantitative understanding of ERAP/IRAP antigen processing and its functional consequences. - Characterise how ERAP/IRAP modulation and variation underlie antigen processing dysfunctions in diseases. - Validate ERAP/IRAP as targets, develop pharmacological probes and bridge their early-stage development all the way to preclinical leads in diseases of urgent medical need. To reach these objectives, CAPSTONE delivered an international and interdisciplinary research and training programme for 15 early-stage researchers (ESRs) and prepared them for a career in academia or the pharmaceutical industry.

Data: CORDIS, © European Union

Project objective

Current trends in immunotherapy are to develop immuno-modulatory small molecules for intracellular targets for single therapy or combination with existing treatments. CAPSTONE scientists have recently identified the key pathway of intracellular antigen processing for modulating the immune response. ERAP enzymes that generate antigenic peptides have thus emerged as promising targets for the cancer immunotherapy and autoimmune diseases treatments. Our innovative research approach based on ERAP, targets the upstream molecular events that cause these diseases. We aim at fully understanding this pathway, deciphering the mechanisms of antigen processing dysfunctions in diseases, and developing innovative therapeutic drugs. This will provide unique opportunities for future treatment of unmet medical needs and innovative immunotherapies. CAPSTONE will thus be an excellent scientific environment to train the next generation of 15 Early Stage Researchers (ESRs) and establish an innovative cross-fertilisation between oncology and auto-immunity. Our fellows will be able to perform outstanding research at the forefront of transdisciplinary science within a high-calibre international network of academics, industries and patient associations. CAPSTONE brings together an intersectorial and multidisciplinary group of researchers in medicinal chemistry, X-Ray crystallography, cellular biology, oncology, autoimmunity, bioanalysis, mass spectrometry imaging, formulation, systems biology, personalised medicine that will expose the ESRs to key R&D stages, from basic research to pre-clinical development. CAPSTONE will prepare the ESRs for exciting career perspectives in academia, the pharmaceutical industry, biotechnology SMEs, and provide them with scientific and transferable skills and high-value professional connections. Industrial secondments and public engagement will add to a broad skill set to ensure employability in the higher ranks of academia and industry.

Original text from CORDIS.

Participants

  • UNIVERSITE DE LILLE · LilleCoordinatorFrance
  • ALIRI FRANCE SAS · LoosFrance
  • ETHNIKO KAI KAPODISTRIAKO PANEPISTIMIO ATHINON · ATHINAGreece
  • INOCURE SRO · PrahaCzechia
  • NATIONAL CENTER FOR SCIENTIFIC RESEARCH ""DEMOKRITOS"""" · Agia ParaskeviGreece
  • NOVAMECHANICS LIMITED · NicosiaCyprus
  • OSPEDALE PEDIATRICO BAMBINO GESU · ROMAItaly
  • UNIVERSITAIR MEDISCH CENTRUM UTRECHT · UtrechtNetherlands
  • UNIVERSITE PARIS CITE · ParisFrance
  • UNIVERSITY OF SOUTHAMPTON · SOUTHAMPTONUnited Kingdom

Links

Data: CORDIS, © European Union