Periodic Reporting for period 1 - OncoProTools (Protease‐guided tumor targeting tools to revolutionize cancer diagnosis and treatment.)
Período documentado: 2022-09-01 hasta 2024-08-31
Cancer is of concern to us all: in 2023, 2.8 million European citizens were diagnosed with the disease and 1.4 million lost their lives to it. Without additional action, the annual death burden is set to increase with 20% by 2035, making cancer the leading cause of death in the EU. Cancer hugely impacts patients, those around them, health systems and also on the European economy: conservative estimates value the financial cost to be in the order of € 100 B/year.
Reflecting this dire situation, the European Commission has launched an international R&D agenda for cancer: Europe’s Beating Cancer Plan (EBCP)[1]. Innovative, patient-centered technologies for cancer diagnosis and treatment are a cornerstone of the EBCP: drastic improvement in patients’ quality-of-life should come, among others, from drugs that more selectively ‘hit’ tumors. This should minimize exposure of healthy tissue and maximize the impact on the disease. Many future cancer diagnostics and therapeutics can therefore be expected to be ‘vectorized’, i.e. to contain a vector moiety that selectively transports the drug to the tumor. Ideally, a vector unit linked to a therapeutic or diagnostic payload should tightly bind to a protein that is abundantly present inside tumors. This will cause the payload to accumulate in the tumor. Several of the most exciting recent innovations rely on vectors that bind to tumoral proteases. Proteases are a class of proteins, many of which are produced in large quantities by tumor cells. Most interestingly, proteases contain ‘anchoring’ sites to which vectors can hook up with very high affinity.
OncoProTools discovers innovative protease targeting vector technologies and applies them for better cancer diagnosis and treatment in a personalized framework. The network has the following specific goals:
(1) Explore innovative cellular immunotherapy strategies, based on protease targeting.
(2) Discover novel vectors that bind to currently underexplored tumor proteases.
(3) Allow protease targeting applications that are tailored to the needs of individual patients, through a deeper understanding of tumor biology.
OncoProTools unites leading academic and industrial experts in oncology and cancer diagnostics, medicinal chemistry and chemical biology, radiochemistry and nano-engineering. Translation of results to real-life applications is empowered via the participation of both clinical researchers and feedback from cancer patients.
*[1] https://ec.europa.eu/health/sites/default/files/non_communicable_diseases/docs/eu_cancer-plan_en.pdf(se abrirá en una nueva ventana)
Reflecting this dire situation, the European Commission has launched an international R&D agenda for cancer: Europe’s Beating Cancer Plan (EBCP)[1]. Innovative, patient-centered technologies for cancer diagnosis and treatment are a cornerstone of the EBCP: drastic improvement in patients’ quality-of-life should come, among others, from drugs that more selectively ‘hit’ tumors. This should minimize exposure of healthy tissue and maximize the impact on the disease. Many future cancer diagnostics and therapeutics can therefore be expected to be ‘vectorized’, i.e. to contain a vector moiety that selectively transports the drug to the tumor. Ideally, a vector unit linked to a therapeutic or diagnostic payload should tightly bind to a protein that is abundantly present inside tumors. This will cause the payload to accumulate in the tumor. Several of the most exciting recent innovations rely on vectors that bind to tumoral proteases. Proteases are a class of proteins, many of which are produced in large quantities by tumor cells. Most interestingly, proteases contain ‘anchoring’ sites to which vectors can hook up with very high affinity.
OncoProTools discovers innovative protease targeting vector technologies and applies them for better cancer diagnosis and treatment in a personalized framework. The network has the following specific goals:
(1) Explore innovative cellular immunotherapy strategies, based on protease targeting.
(2) Discover novel vectors that bind to currently underexplored tumor proteases.
(3) Allow protease targeting applications that are tailored to the needs of individual patients, through a deeper understanding of tumor biology.
OncoProTools unites leading academic and industrial experts in oncology and cancer diagnostics, medicinal chemistry and chemical biology, radiochemistry and nano-engineering. Translation of results to real-life applications is empowered via the participation of both clinical researchers and feedback from cancer patients.
*[1] https://ec.europa.eu/health/sites/default/files/non_communicable_diseases/docs/eu_cancer-plan_en.pdf(se abrirá en una nueva ventana)
Within OncoProTools, 10 Doctoral Candidates perform cutting-edge research. They collaborate in 3, cross-talking Work-Packages (WPs) that each focus on 1 of the project goals.
1) WP1 develops safer and more effective CAR T cell therapy. OncoProTools researchers have already developed protease-targeting molecules that allow CAR T cells to more selectively release their deadly cargo inside tumors, while not exposing healthy tissue. The new molecules are now being thoroughly studied in in vitro models. Among others, WP1 researchers use an innovative, nanotechnology-based approach developed in WP3, to study the selective cancer-killing efficacy of their CAR T cells. In addition, WP1 researchers are exploring the possibility to combine their optimized CAR T cell approaches with novel forms of vectorized endoradiotherapy and chemotherapy, in order to obtain maximally selective therapies with unprecedented efficacy.
2) In WP2, our researchers develop new vector moieties for currently underexplored tumor proteases. Several promising new series of molecules have already been delivered. After a thorough in vitro characterization, the first new molecules are now being investigated on an advanced preclinical level: among others, their tumor targeting potential is determined. This is done by attaching a radioactive label to the molecules. The label allows tracking molecules inside living organisms suffering from cancer, relying on Positron Emission Tomography (PET imaging). Of note, several of these molecules can be used to follow up patients treated with cellular immunotherapy, making further co-development with WP1 and WP3 technologies realistic.
3) In WP3, our researchers gather fundamental insights into the biology of tumor proteases: they try to identify factors that determine which proteases are present in tumors, and in which amounts. This knowledge will allow identifying the most suited vector technologies for individual patients and for different stages of disease. Among others, WP3 research has already allowed a new radiopharmaceutical from one of our industrial project partners, to enter systematic clinical investigation in patients with hard-to-treat cancers. Moreover, WP3 researchers have found a way for applying their nanotechnology-based tumor characterization device, to the study of the optimized CAR T cells, in collaboration with WP1 researchers.
1) WP1 develops safer and more effective CAR T cell therapy. OncoProTools researchers have already developed protease-targeting molecules that allow CAR T cells to more selectively release their deadly cargo inside tumors, while not exposing healthy tissue. The new molecules are now being thoroughly studied in in vitro models. Among others, WP1 researchers use an innovative, nanotechnology-based approach developed in WP3, to study the selective cancer-killing efficacy of their CAR T cells. In addition, WP1 researchers are exploring the possibility to combine their optimized CAR T cell approaches with novel forms of vectorized endoradiotherapy and chemotherapy, in order to obtain maximally selective therapies with unprecedented efficacy.
2) In WP2, our researchers develop new vector moieties for currently underexplored tumor proteases. Several promising new series of molecules have already been delivered. After a thorough in vitro characterization, the first new molecules are now being investigated on an advanced preclinical level: among others, their tumor targeting potential is determined. This is done by attaching a radioactive label to the molecules. The label allows tracking molecules inside living organisms suffering from cancer, relying on Positron Emission Tomography (PET imaging). Of note, several of these molecules can be used to follow up patients treated with cellular immunotherapy, making further co-development with WP1 and WP3 technologies realistic.
3) In WP3, our researchers gather fundamental insights into the biology of tumor proteases: they try to identify factors that determine which proteases are present in tumors, and in which amounts. This knowledge will allow identifying the most suited vector technologies for individual patients and for different stages of disease. Among others, WP3 research has already allowed a new radiopharmaceutical from one of our industrial project partners, to enter systematic clinical investigation in patients with hard-to-treat cancers. Moreover, WP3 researchers have found a way for applying their nanotechnology-based tumor characterization device, to the study of the optimized CAR T cells, in collaboration with WP1 researchers.
OncoProTools delivers 3 asset types that go significantly beyond the state-of-the-art:
1) New vector molecules that target tumoral proteases.
2) Significantly improved technology for cellular immunotherapy.
3) Knowledge on, and innovative technology for maximally patient-tailored cancer management.
Relevant examples of results that have been obtained at this project stage were already provided in the foregoing section. They comprised > 5 innovative, protease targeting vectors with optimal in vitro performance. If their tumor homing potential is confirmed in vivo (via PET imaging), the same molecules can readily be used for tumor-selective delivery of toxic cancer drugs. Likewise, the optimized CAR T immunotherapies that have been developed will now be further elaborated and studied in cancer models of increasing complexity. Finally, the fundamental insight into the biological aspects of specific tumor proteases has already allowed a novel protease-vectorized radiotherapeutic from our industrial partner, to enter systematic clinical trials. In this way, the project has already directly created an impact for cancer patients. Likewise, the nanotechnology-based technology platform from our industrial Beneficiary CellPly already implements patient-derived samples.
Also during the second part of the project, OncoProTools will rely on its exploitation and commercialization roadmap to further increase project impact. This should lead to the following tangible results, for which strong foundations have now been laid:
-economic & technological: new business cases for Europe’s R&D sector.
-societal impact: better cancer management for European cancer patients.
1) New vector molecules that target tumoral proteases.
2) Significantly improved technology for cellular immunotherapy.
3) Knowledge on, and innovative technology for maximally patient-tailored cancer management.
Relevant examples of results that have been obtained at this project stage were already provided in the foregoing section. They comprised > 5 innovative, protease targeting vectors with optimal in vitro performance. If their tumor homing potential is confirmed in vivo (via PET imaging), the same molecules can readily be used for tumor-selective delivery of toxic cancer drugs. Likewise, the optimized CAR T immunotherapies that have been developed will now be further elaborated and studied in cancer models of increasing complexity. Finally, the fundamental insight into the biological aspects of specific tumor proteases has already allowed a novel protease-vectorized radiotherapeutic from our industrial partner, to enter systematic clinical trials. In this way, the project has already directly created an impact for cancer patients. Likewise, the nanotechnology-based technology platform from our industrial Beneficiary CellPly already implements patient-derived samples.
Also during the second part of the project, OncoProTools will rely on its exploitation and commercialization roadmap to further increase project impact. This should lead to the following tangible results, for which strong foundations have now been laid:
-economic & technological: new business cases for Europe’s R&D sector.
-societal impact: better cancer management for European cancer patients.