Periodic Reporting for period 1 - INsTRuCT (INnovative Training in Myeloid Regulatory Cell Therapy)
Reporting period: 2020-01-01 to 2021-12-31
The INsTRuCT Consortium answers the need for scientific and technological innovation in myeloid regulatory cell (MRC)-based therapy research and training. INsTRuCT’s partners from academia and industry have created a framework for advancing original basic scientific discoveries into novel cell products and processes, which will lead to higher quality immune therapies.
MRC-based therapies represent an attractive strategy for treating autoimmune diseases and transplant rejection. Because MRC-based therapy has the potential to induce antigen-specific immune non-reactivity, it could be used to treat the root cause of immune-mediated diseases, sparing the toxic effects of general immunosuppression. Moreover, because MRC-based therapy can induce a self-reinforcing immune regulation, its clinical effects could be very long-lived. Hence, MRC-based therapy opens the remarkable possibility of curative treatments for common diseases that must otherwise be managed with long-term, general immunosuppression. First-generation MRC-based cell therapies are now being investigated in early-phase clinical trials across a broad range of indications, including solid organ transplantation, rheumatoid arthritis (RA) and multiple sclerosis (MS). Preliminary success in these proof-of-principle studies justifies their further pharmaceutical development, hopefully leading to their implementation as routine medical treatment over the next 10 to 20 years.
MRC-based therapies represent an attractive strategy for treating autoimmune diseases and transplant rejection. Because MRC-based therapy has the potential to induce antigen-specific immune non-reactivity, it could be used to treat the root cause of immune-mediated diseases, sparing the toxic effects of general immunosuppression. Moreover, because MRC-based therapy can induce a self-reinforcing immune regulation, its clinical effects could be very long-lived. Hence, MRC-based therapy opens the remarkable possibility of curative treatments for common diseases that must otherwise be managed with long-term, general immunosuppression. First-generation MRC-based cell therapies are now being investigated in early-phase clinical trials across a broad range of indications, including solid organ transplantation, rheumatoid arthritis (RA) and multiple sclerosis (MS). Preliminary success in these proof-of-principle studies justifies their further pharmaceutical development, hopefully leading to their implementation as routine medical treatment over the next 10 to 20 years.
The INsTRuCT Consortium has structured its research and training concept around the four major phases of drug development, namely – basic scientific investigation, manufacturing technology, preclinical development, and clinical testing (Figure). Through interdisciplinary and intersectoral collaborations, INsTRuCT is accelerating MRC-based therapy by carrying forward innovations from one development stage to the next. Specifically, INsTRuCT has made important advances in four areas:
Innovative approaches for generating MRC cell products with greater stability and potency
ESR projects 1-4 and 14 have advanced our understanding of how cellular metabolism influences differentiation of monocytes into MRC. Transcriptomic, epigenetic and functional screening experiments have identified novel molecules and pathways involved in development and stabilization of MRC phenotype and function.
Developing more reliable and affordable manufacturing procedures for MRC-based therapies
ESR projects 5, 7, 8 and 11 have mapped the steps involved in manufacturing of MRC-based therapies, which allows us to better understand the factors contributing to variation in the pharmaceutical quality of MRC products.
Pharmacological characterization of MRC-based cell products
ESR projects 6, 12 and 14 have led to technological developments and new insights into the tissue distribution and immunological functions of MRC after administration.
Innovative approaches for generating MRC cell products with greater stability and potency
ESR projects 1-4 and 14 have advanced our understanding of how cellular metabolism influences differentiation of monocytes into MRC. Transcriptomic, epigenetic and functional screening experiments have identified novel molecules and pathways involved in development and stabilization of MRC phenotype and function.
Developing more reliable and affordable manufacturing procedures for MRC-based therapies
ESR projects 5, 7, 8 and 11 have mapped the steps involved in manufacturing of MRC-based therapies, which allows us to better understand the factors contributing to variation in the pharmaceutical quality of MRC products.
Pharmacological characterization of MRC-based cell products
ESR projects 6, 12 and 14 have led to technological developments and new insights into the tissue distribution and immunological functions of MRC after administration.
Studying the impact of patient-related factors on the effectiveness of MRC-based therapies
Through sharing know-how and results within the consortium, ESR projects 9, 10, 13 and 15 made important advances towards establishing assays to stratify patients prior to therapy according to their predicted responses or to measure the immunological effects of MRC-based therapies in patients.
The INsTRuCT Consortium has already made a substantial scientific, societal and economic impact. Within the network, 15 early-stage researchers were recruited as MSCA Fellows to study for PhD titles. Collectively, their research has contributed to 14 scientific publications in major journals, including The Lancet, Cell, Nature Communications, Cellular & Molecular Immunology and Cell Reports. Scientific results from the project are already being exploited through direct applications in clinical research or commercial development. INsTRuCT partners are committed to communicating about their work with the general public, patient advocacy groups and policy makers. Through its online presence and outreach activities, the INsTRuCT Consortium is actively promoting the importance of scientific research supported by the European Union for the advancement of society.
Through sharing know-how and results within the consortium, ESR projects 9, 10, 13 and 15 made important advances towards establishing assays to stratify patients prior to therapy according to their predicted responses or to measure the immunological effects of MRC-based therapies in patients.
The INsTRuCT Consortium has already made a substantial scientific, societal and economic impact. Within the network, 15 early-stage researchers were recruited as MSCA Fellows to study for PhD titles. Collectively, their research has contributed to 14 scientific publications in major journals, including The Lancet, Cell, Nature Communications, Cellular & Molecular Immunology and Cell Reports. Scientific results from the project are already being exploited through direct applications in clinical research or commercial development. INsTRuCT partners are committed to communicating about their work with the general public, patient advocacy groups and policy makers. Through its online presence and outreach activities, the INsTRuCT Consortium is actively promoting the importance of scientific research supported by the European Union for the advancement of society.