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Bone Cancer Research Trust Strictly Research Grant Applications 07/05/2016 BCRT 10 th Anniversary Conference CHARITABLE INCORPORATED ORGANISATION (CIO) NUMBER - 1159590 Evaluation of a novel MT1-MMP activated ferrous nanoparticle as a


  1. Bone Cancer Research Trust ‘Strictly Research’ Grant Applications 07/05/2016 BCRT 10 th Anniversary Conference CHARITABLE INCORPORATED ORGANISATION (CIO) NUMBER - 1159590

  2. Evaluation of a novel MT1-MMP activated ferrous nanoparticle as a theranostic and surgery planning tool in Ewing sarcoma and osteosarcoma Kenneth Rankin, H Blair, E Haagensen, C Gerrand, R Maxwell & A Blamire (Newcastle) & Jason Gill (Durham)

  3. Background • Our options for up to one third of patients with osteosarcoma and Ewing’s sarcoma are still not good enough • There are no new treatments on the horizon (within 5 years from now) • Exploiting Membrane type-1 matrix metalloproteinase (MT1-MMP) may be a way forward • Our collaboration presents a promising opportunity to develop a new way of treating patients

  4. Who’s involved? • Kenny Rankin: Orthopaedic surgeon/scientist • Craig Gerrand: Orthopaedic surgeon • Emma Haagensen: Scientist • Helen Blair: Scientist • Ross Maxwell: Expert in imaging cancers • Andrew Blamire: Magnetic Resonance Physicist • Jason Gill: Pharmacologist

  5. BONE OS Cell Osteoblast MT1-MMP Stem cell MT1-MMP Basement proMMP-2 TIMP-2 membrane MMP-2 Blood vessel

  6. Question to be answered Osteosarcoma- strong staining Ewing sarcoma- very strong staining Chondrosarcoma- weak staining Given that MT1- MMP is produced in large amounts by osteosarcoma and Ewing’s sarcoma cells. Can we use our new ‘theranostic’ agent to more effectively treat patients with osteosarcoma and Ewing sarcoma?

  7. Theranostic= diagnostic + therapeutic MT1-MMP activation site ICT Ferrous nanoparticles linker Peptide MT1-MMP

  8. Time for the pre-operative MRI scan ICT ICT

  9. How will we answer the question? In vitro testing • Growing osteosarcoma and Ewing’s cells in a dish and assessing the effectiveness of the ICT at killing them In vivo testing • Assessing how effective the MT1-MMP activated theranostic is at treating mice that have been implanted with osteosarcoma and Ewings’ sarcoma • Doing MRI scans on the mice to see how effective the theranostic improves the scan quality

  10. Justification for funding • We are requesting funds to make enough of the MT1-MMP activated theranostic to complete the whole program of work • Costs for doing the in vitro and in vivo work are in place at our Institute from local charities

  11. How long will it take? • We expect to complete the main body of work within 2 years • This includes publication of the results

  12. The End Goal • The MT1-MMP activated ICT drug is not toxic to normal cells or the cardiovascular system • The ferrous nanoparticles are already approved in the USA for use in other diseases • We therefore expect that this treatment could be introduced into clinical trials for osteosarcoma and Ewing’s as soon as 3 years time

  13. Thank you Any Questions? Kenneth Rankin on behalf of the research team

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