Summary
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.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/963953 |
| Start date: | 01-05-2021 |
| End date: | 31-10-2022 |
| Total budget - Public funding: | - 150 000,00 Euro |
Cordis data
Original description
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.Status
CLOSEDCall topic
ERC-2020-POCUpdate Date
27-04-2024
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