ChipCytometry

Welcome!

Agenda

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• 10:30 Arrival at Peter Medawar Building for Pathogen Research • 10:45 Chris Willberg: Welcome reception, introduction • 11:15 Christian Hennig: Introduction to Chipcytometry, Deep

Phenotyping and Tissue Cytometry • 11:45 Matthew Bilton: Analysis of MAIT cell populations within

mediastinal lymph nodes. • 12:15 Jan Detmers: Chipcytometry in a clinical setting • 12:30 Lunch • 13:15 visiting the lab • 14:00 Christian Hennig: Chipcytometry case studies, Q&A • 15:30 End of meeting

About

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Zellkraftwerk GmbH

• Hannover, Germany

• 2 Divisions: Instrument Manufacturer – CRO

• CRO: Currently 4 phase I; 2 phase II trials

VA Partner

Central Lab Services

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Fully automated analyzer

24/7 operation

4,000 data points/week

“Spirit of GLP”

Global Footprint

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Sponsor

Central Lab BioBank ZellSafe™Box World Courier

Case Study (opticus neuritis)

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Clinical Neuroimmunology

Clinical Neuroimmunology

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- Disease: Multiple Scler.

- Study: Clinical

- Samples: 650

1. Round 2. Round

Outcome: - Stratification markers - Trial is ongoing

By courtesy of

Work Flow

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2. Load - Load sample, wait 5‘ - Fix (4% PFA), wait 15‘ - rinse, seal chip

1. Prep - 1 ml blood - CPT, Ficoll or RBC lysis - total time: 40’

3. Store - store on-site - temperature 4°C - up to several months

4. Ship GDP Logistics (Good Distribution Practice)

5. Bioanalysis “Spirit of GLP” clinical trial

support (SOP, QA)

6. Re-interrogate Test additional markers over >24 months

Cell-based Biomarker Development

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1: Study Preparation Phase

• SOP / Training Videos / Site Qualification

• On-site Training

2: Sample Collection Phase

• Custom kits with all consumables required

• Monthly / bi-monthly / quarterly sample pick-up according GDP

• Incoming sample QC and bio-banking analogous to GLP

3: Bioanalysis

• Assay / Method Development

• Method Validation analogous to GLP

• Sample analysis including ISR

• Option for sample re-interrogation for 24 months

4: Patient Stratification and Computational Biology

Preparing Clinical Trials

Candidate Sites 1, 2, 3, 4,..

2. Site Qualification Kit

1. SOP, Training Video

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Collaborative Cytometry

Core Facility „Democratization“ Collaborate („go to an expert“) („have your own“) (“work with many”)

IT

FACS

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Biomarker Development

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Clinical Research Center Hannover

Method Development • Preanalytics • Assay Development • Data Processing • Data Management

Pilot Preparation

Planning • Study plan / IPC • IRB • Clinical Database • Site Audit

Clinical trial

Execution • Study Coordinator • Data Collection • Sample Analysis • Sample Logistics • Biobanking

Typical Milestone-based Project

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Study Validation In-Study

Bioanalysis Work

Plan Panel Set-up

+ Controls

Samples Ideas

Thank you for your attention!

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Selected Primary Publications

• Happle, Science Translational, 2014

• Dijkstra, Nature Medicine 2012

• Hennig, Br. J. Hematology 2010

• Woelbeling, Immunobiology 2011

• Polte, JACI 2008

System Validation according to:

• O'Hara, JIM 2011

• Green, JIM 2011

• Cunliffe, Pharm. Res. 2009

• Lee, Pharm. Res. 2006

• Bioanalytical Method Validation, FDA, 2013

“Precision Immunology” References

A B C Control Diseased Groups Group

Focus on: Translational Immunology Mode of Action(MoA) Patient Stratification Clinical Trial Support