Project description
Exploring a class of “aggressive” particles as a novel therapy for cancer
Upon attack, cytotoxic T lymphocytes and natural killer cells release supramolecular attack particles (SMAPs), which contain perforin and granzymes and can function autonomously for up to 24 hours after release. The EU-funded SMAPCAN project proposes to engineer SMAPs as a novel particle-based therapy against cancer. The idea is to deliver SMAPs to surgical sites to destroy residual disease after resection and prevent tumour recurrence. Researchers will evaluate the efficacy of SMAPs on glioblastoma and ovarian carcinoma cells and test their in vivo biodistribution and toxicity in mouse models of these diseases.
Objective
Supramolecular attack particles (SMAPs) are proteinaceous particles ~120 nm in diameter released from cytotoxic T cell and natural killer cells. The particles have a core of cytotoxic proteins including perforin andgranzymes enveloped in a dense shell of glycoproteins including thrombospondin-1, which provides specificity for SMAP mediated killing. SMAPs released from T-cells are stable for at least 24 hours and can kill target cells autonomously. The human cell line NK92 secretes SMAPs based on inclusion of perforin and granzyme B. We have filed a patent on SMAP engineering and isolation and propose to work with experts in glioblastoma (GBM) and ovarian high-grade serous carcinoma (OC), and with interest from a biotech company with expertise in particle based therapies, to develop SMAPs as cancer therapies. GBM and OC are both diseases with high unmet need that are treated by surgical resection followed by chemo-radiation and patients succumb to local recurrence. GBM and OC don’t respond to immunotherapies. As SMAPs are autonomously cytotoxic and can readily be delivered to surgical sites to destroy residual disease after resection we see an opportunity to develop SMAPs as therapies to reduce recurrence. The next step after SYNECT completion will be to determine if SMAPs can be used to attack the tumour selectively without damage to normal tissues. We request funding to enrich SMAPs from NK92 cells supernatants and test these against GBM and OC cell lines in vitro. We will also label SMAPs with fluorescent dyes and test biodistribution and toxicity in mouse models of intravenous, intracranial and intra-peritoneal injection. This 1 year effort will enable mathematical modelling to design efficient preclinical studies in humanized mouse models in one or both of these indications that will be funded by future grants or private sector investment. These results will also enable refinement of intellectual property, value creation and commercialization plans.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine immunology immunotherapy
- natural sciences mathematics applied mathematics mathematical model
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
ERC-POC - Proof of Concept Grant
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2020-PoC
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
OX1 2JD Oxford
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.