AMC Alex Kerr Presentation %5bAutosaved%5d · ] } u ] o Z Z v ' µ Ç [ v ^ d Z } u [ E,^ & } µ v...

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Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London CD16+ Monocyte Cell Therapy to Prevent Amputation in Critical Limb Ischaemia Alex Kerr Senior Advanced Therapy Production Scientist NIHR Clinical Research Facility Guy’s and St Thomas’ NHS Foundation Trust and King’s College London PIs: Mr Ashish Patel PhD FRCS Mr Bijan Modarai PhD FRCS

Transcript of AMC Alex Kerr Presentation %5bAutosaved%5d · ] } u ] o Z Z v ' µ Ç [ v ^ d Z } u [ E,^ & } µ v...

Page 1: AMC Alex Kerr Presentation %5bAutosaved%5d · ] } u ] o Z Z v ' µ Ç [ v ^ d Z } u [ E,^ & } µ v ] } v d µ v < ] v P [ } o o P > } v } v

Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London

CD16+ Monocyte Cell Therapy to Prevent Amputation in Critical Limb IschaemiaAlex KerrSenior Advanced Therapy Production ScientistNIHR Clinical Research FacilityGuy’s and St Thomas’ NHS Foundation Trust and King’s College London

PIs: Mr Ashish Patel PhD FRCSMr Bijan Modarai PhD FRCS

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Biomedical Research Centre At Guy’s and St Thomas’ NHS Foundation Trust and King’s College London

BD Miltenyi BiotecCritical Limb Ischaemia• 20% of patients > 70yrs have peripheral vascular disease• Conventional treatments only benficial in ~50%• 5-10% progress to critical limb ischaemia (CLI)

Major vessels occluded Ischaemic tissue Gangrene

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Biomedical Research Centre At Guy’s and St Thomas’ NHS Foundation Trust and King’s College London

Conventional Treatment

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Biomedical Research Centre At Guy’s and St Thomas’ NHS Foundation Trust and King’s College London

Collateralisation

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Biomedical Research Centre At Guy’s and St Thomas’ NHS Foundation Trust and King’s College LondonFurmston & Patel AS et al., J Cardiovasc Surg, 2014

Therapeutic Neovascularisation

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Biomedical Research Centre At Guy’s and St Thomas’ NHS Foundation Trust and King’s College London

BD Miltenyi BiotecMonocytes“Non-Classical”

“Intermediate”

“Classical”

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Biomedical Research Centre At Guy’s and St Thomas’ NHS Foundation Trust and King’s College London

BD Miltenyi BiotecCD16+ Monocytes are Angiogenicin vitro and in vivo

Control CD16+CD16-

* *ns

Control CD16+ CD16- Control CD16+ CD16-

* *ns

HUVEC Matrigel Assay CD16- CD16+

CD16+ monocytes

CD16- monocytes

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Biomedical Research Centre At Guy’s and St Thomas’ NHS Foundation Trust and King’s College London

BD Miltenyi BiotecPre-Clinical Isolation

CD14

CD16

2. Negative depletionof CD56+ cells

4. Positive selection(CD14 Microbeads)

1. Ficoll preparation to isolate PBMCs

PBMCs

CD14

CD16

CD14

CD16

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Biomedical Research Centre At Guy’s and St Thomas’ NHS Foundation Trust and King’s College London

BD Miltenyi BiotecGMP Isolation

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Biomedical Research Centre At Guy’s and St Thomas’ NHS Foundation Trust and King’s College London

BD vs. Miltenyi BiotecRetention of Angiogenic Monocytes in CLI (ROAM-CLI) Physiological StudyLeukaphaeresis at King’s College Hospital

Overnight Cell Isolation

Day 1, Monday

Day 2, Tuesday

Day 4, Wednesday

Day 5, Friday 30 minute scan at Nuclear Medicine, Guy’s Hospital

Home

30 minute scan at Nuclear Medicine, Guy’s Hospital

Home

Injection of cells and 30 minute scan atNuclear Medicine, Guy’s Hospital

Home

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Biomedical Research Centre At Guy’s and St Thomas’ NHS Foundation Trust and King’s College London

BD vs. Miltenyi BiotecPatient 186yrs oldRutherford Scale 5- rest pain- heel ulcer- dusky toes“No option”Planned for AKA

30 mins Post- Cell Delivery

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24 hours 3 days

Injection site: 66% of whole-bodyUpper body: 22% of whole-body Injection site: 52% of whole-bodyUpper body: 31% of whole-bodyBiomedical Research Centre At Guy’s and St Thomas’ NHS Foundation Trust and King’s College London

Cell Distribution

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Patient No.Startingproduct total cells(x108)

Lymphocytes (%) Monocytes (%)Totals cells final product(x106)

Viability (%) CD16+ cells (%) Sterility

1 8164 N/A N/A 340 88 69 No Growth after 5 days2 13600 80 20 233 92 65 No Growth after 5 days3 12292 49 41 217 97 80 No Growth after 5 days

4 24360 56 42 177 97 63 No Growth after 5 days

5 34816 60 40 170 96 73 No Growth after 5 days

Average 18646 61 36 227 94 70

Biomedical Research Centre At Guy’s and St Thomas’ NHS Foundation Trust and King’s College London

Study Summary

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Biomedical Research Centre At Guy’s and St Thomas’ NHS Foundation Trust and King’s College London

BD vs. Miltenyi Biotec

• Prodigy scale-up• FACS• Multiple injections• Isolate heterogeneous monocytes (CD14+), then

skew towards pro-angiogenic phenotype in culture

Future Work

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Biomedical Research Centre At Guy’s and St Thomas’ NHS Foundation Trust and King’s College London

AcknowledgementsAshish Patel Clinical Lecturer in Vascular SurgeryBijan Modarai Reader/BHF Senior Fellow in Vascular SurgeryAcademic Department of Vascular Surgery, King’s College London

Drew HopeChris FisherLaura FryJulie HewardAlex Beese-HernandezNIHR Clinical Research Facility, Guy’s and St Thomas’ NHS Foundation Trust and King’s College London


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