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

CHARITABLE INCORPORATED ORGANISATION (CIO) NUMBER - 1159590

Bone Cancer Research Trust

‘Strictly Research’ Grant Applications

BCRT 10th Anniversary Conference 07/05/2016

Kenneth Rankin, H Blair, E Haagensen, C Gerrand, R Maxwell & A Blamire (Newcastle) & Jason Gill (Durham)

Evaluation of a novel MT1-MMP activated ferrous nanoparticle as a theranostic and surgery planning tool in Ewing sarcoma and

• steosarcoma

Background

• Our options for up to one third of patients with
• steosarcoma 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

Osteoblast

MT1-MMP Basement membrane Blood vessel

Stem cell

proMMP-2 TIMP-2 MMP-2 OS Cell MT1-MMP BONE

Question to be answered

Chondrosarcoma- weak staining Osteosarcoma- strong staining Ewing sarcoma- very strong 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

• steosarcoma and Ewing sarcoma?

ICT

MT1-MMP activation site

Ferrous nanoparticles

MT1-MMP Theranostic= diagnostic + therapeutic Peptide linker

ICT ICT

Time for the pre-operative MRI scan

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
• ur 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

Kenneth Rankin on behalf of the research team

Thank you Any Questions?