Bone Cancer Research Trust Strictly Research Grant Applications - PowerPoint PPT Presentation

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 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)

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

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

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

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?

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

Time for the pre-operative MRI scan ICT ICT

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

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

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

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

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