Automatisierung von CAR Effektorzellen · * A conflict of interestis any situation in which a...

© Fraunhofer IZI

Automatisierung von CAR Effektorzellen

Ulrike Köhl

14.09.2018

Institute of Cellular Therapeutics, Hannover Medical School (MHH) Fraunhofer Institute for Cellular Therapeutics and Immunology (IZI),

Institute of Clinical Immunology, University of Leipzig (UL/UKL), GermanyUKLUL

© Fraunhofer IZI

In relation to this presentation, I declare that there are no conflicts of interest.*

“CD20CAR-TIME“ is a joint research project partly funded by the German ministry ofeducation and research (ref. 01EK1507A-C) within the research programme“Innovations in Personalised Medicine“.

* A conflict of interest is any situation in which a speaker or immediate family members have interests, and those may cause a conflictwith the current presentation. Conflicts of interest do not preclude the delivery of the talk, but should be explicitly declared. Thesemay include financial interests (e.g. owning stocks of a related company, having received honoraria, consultancy fees), researchinterests (research support by grants or otherwise), organisational interests and gifts.

Disclosure

Köhl 2.3.2017

http://www.miltenyibiotec.com/

© Fraunhofer IZI

Network cell and gene therapy - manufacturingDirector/Head ICT, ICI, IZI: Prof. Dr. U. Köhl

I. Hannover Medical School, Hannover (MHH)Institute of Cellular Therapeutics (ICT)

II. University and University Hospital Leipzig (UL/UKL)Institute of Clinical Immunology (ICI)

III. Fraunhofer Institute for Cellular Therapeuticsand Immunology (IZI), Leipzig

Köhl 27.06.2017

UKL

IZI

UKLUL

Germany

MHH

IZI

CancerAdipositas

TransplantationRegeneration

© Fraunhofer IZI

GMP Cell and Gene Therapy Manufacturing Units

MHH GMP Core facility, ICT 3 clean rooms “A in B”

Head: Dr. L. Arseniev

21 qualified staff members

GMP Development Unit (GMPDU): Up-Scaling

Cellular Therapy Centre (CTC): Manufacturing

IZI GMP Core facility 3 facilities, 21 clean rooms („A in B“, level S2)

Head: Dr. G. Schmiedeknecht

> 100 qualified staff members

Cross-link to the IZI development units

© Fraunhofer IZI

IZI: > 600 staff members/ 3.508 m² lab/ additional 5 sub institutes

Clinical StudiesPhase I/ II/ III/ IVGMP ManufacturingPre-clinical development

Development up to translation into the clinic

© Fraunhofer IZI

Manufacturing of cell-based therapies

Pre-clinical Manufacturing and proof „AMG“Late clinical

studies„First in man“

study

Blood and bone marrow stem cells (incl. CD34 sel., CD3/CD19 depl., TCR α/ß depl.)

CAR T cells Melanoma

Regulatory T cells

Antigen-specific T cells (CMV-, ADV-, EBV-, multivirus-spec. CTL)

iPS-cardiomyocytes

Mesenchymal stroma cells

CAR NK cells

Dendritic cells

Routine

Europe wide

CAR = Chimeric Antigen Receptor iPS = induced pluripotent stem cells

iPS-macrophages

CD19 CAR T cells (CTL019)

> 350 cellular products/ year

Clinical andIndustrial partners

http://www.novartis.de/index.shtmlhttp://www.nwbio.com/about_overview.php

© Fraunhofer IZI

Chimeric antigen receptor

(CAR)

“CAR” expressing effector cells

CAR engineered T cells- clininical studies- manufacturing challenge

„off the shelf“ CAR NK cells

- clinical NK cell studies- primary human „CAR“ NK cells- lytic activity- benefit and side effects

Retargeted T cell

NK = Natural Killer

Köhl 2.3.2018

GD2ErbB2CD19CD20

CD123CD44v6

CARanti-GD2

anti-ErbB2anti-CD19anti-CD20

anti-CD123anti-CD44v6

© Fraunhofer IZI

Clinical trials with CAR expressing T cells(clingov. Q4/2016)

Zuther K … Koehl U. J Onkologie 2017

79% 66%

Europe9 Studies

296 Patients

Israel1 Study

40 Patients

Japan1 Study

18 Patients

100 open clinical trials with CAR T cells registered worldwide3831 patients should be included:

27%industry

academia73%

Sponsorship

CD19CD20CD22CD30CD33…

38%solidTumors

CD19

CD20ErbBEpCAMGD2GPC3HER2…………Leukemia,

Lymphoma62%

USA39 Studies

2046 Patients

China50 Studies

1431 Patients

Köhl 2.3.2018

Indications and Target-Antigens

Diagramm1

Tabelle1

USA

industry21

academia79

Ziehen Sie zum Ändern der Größe des Diagrammdatenbereichs die untere rechte Ecke des Bereichs.

Diagramm1

Tabelle1

China

industry34

academia66


Diagramm1

Industry

Academy

Verkauf

26

74

Tabelle1

Verkauf

Industry26

Academy74


Diagramm1

Industry

Academy

CD20CD22CD30CD123……..…..

Verkauf

38

62

Tabelle1

Verkauf

Industry38

Academy62


© Fraunhofer IZI

Clinical trials with CAR expressing T cells(clingov. Q4/2016)

Zuther K … Koehl U. J Onkologie 2017

79% 66%

Europe9 Studies

296 Patients

Israel1 Study

40 Patients

Japan1 Study

18 Patients

100 open clinical trials with CAR T cells registered worldwide3831 patients should be included:

27%industry

academia73%

Sponsorship

CD19CD20CD22CD30CD33…

38%solidTumors

CD19

CD20ErbBEpCAMGD2GPC3HER2…………Leukemia,

Lymphoma62%

USA39 Studies

2046 Patients

China50 Studies

1431 Patients

Köhl 2.3.2018

Indications and Target-Antigens

Num

bero

fClin

ical

stu

dies

J. Hartmann, EMBO 2017Update 9/2018: n > 390 studies

Diagramm1

Tabelle1

USA

industry21

academia79


Diagramm1

Tabelle1

China

industry34

academia66


Diagramm1

Industry

Academy

Verkauf

26

74

Tabelle1

Verkauf

Industry26

Academy74


Diagramm1

Industry

Academy

CD20CD22CD30CD123……..…..

Verkauf

38

62

Tabelle1

Verkauf

Industry38

Academy62


© Fraunhofer IZIMaude SL et al. Februar 2018

75 patients

CTL019 pediatric r/r ALL – ELIANA”Event-free” and “overall survival”

Event-free survival• 73% post 6 months• 50% post 12 months

Overall survival• 90% post 6 months• 76% post 12 months

Now > 5 years cured

© Fraunhofer IZI

Marketing authorization in Europe

2017 2018

Kymriah® (EMA)Novartis

27.08.2018

Yescarta® (EMA)

Kymriah® (FDA)Novartis

Yescarta® (FDA)KITE

470.000 €/ product

320.000 €/ product

Marketing authorization CAR T cells (Kymriah®), EU

Press release NOVARTIS - Fraunhofer IZI, 30.8.2018

© Fraunhofer IZI

H Abken

Human Gene Therapy online 1. May 2018

© Fraunhofer IZI

transfer & tare centrifugate extract resuspend dis-/connect

(45 min + 3 dis-/connections) x 15/process = 11¼ hrs + 45 dis-/connectionsexcubate

COBE 2991(Terumo BCT)

SEPAX 2(Biosafe SA)

WAVE(GE Healthcare)

(non-exhaustive)

e.g. PERFUSE / WASH / FORMULATE

SEFIA(Biosafe SA)

State of the art: hands on manufacturing

http://vertassets.blob.core.windows.net/image/4dc43bc8/4dc43bc8-e07d-4d6d-805b-40883b878a78/wave25.jpg

LAB BENCH BEDSIDEENGINEERING EFFECTIVITY

WORKBENCH

• rapid prototyping• robust manufacture

• smallest batches• personalized • regulated environment

efficacy

• limitations• toxicities• timeframes

TOOLMAKER

• vectors (GMP compliant)• raw materials (GMP compatible)• platforms (GMP compatible)

• improved CARs• safer vectors• new / alternative targets

MANUFACTURING EFFICIENTLY

Automated manufacturing?

© Fraunhofer IZI

Start in the Prodigy:Apheresisproduct

Start in the Prodigy:

Immunomagneticselected T cells

Automated manufacturing of CAR T cells

© Fraunhofer IZI


Prodigy

TCT: T cell transduction

Transduktion

S 2

Vektor

1

T-ZellSelektionApheresat

-1

Medium

X

Abfall

3

Medium

X

Abfall

6,8,9

Formulierung

Trägerlsg.

X

Abfall

10…12

Expansion

IPK

X

IPK

Expansion

Medium

5

X

Expansion

IPK

X

Aktivierung

Akt.-Reag

Prodigy

Transduction

Vector

1

T cellSelection

ApheresisProduct

-1 days

X

Waste

X aseptic disconnection (integrated tube sealer) from… centrifugation in and

IPC

Medium

X

Waste

3

Wash

Medium

X

Waste

6,8,(10-12)

Exchange

Formulation

Formulation

Buffer

X

Waste

10-13

Wash

agitation of cultivation chamber of…

Expansion

IPC

X

IPC

Expansion

Medium

5Feed

Addition

X

Expansion

IPC

X

Activation

ActivationReagent

… functionally closed disposable tubing set

aseptic connection (Terumo Sterile Connecting Device) to…

SelectionReagents

Medium

0

Leukapheresis Infusion

results

© Fraunhofer IZI

Köhl 28.03. 2017


melanoma patient Leuka-

pheresis

CD62L or CD4/CD8 selected T cells

Lentiviral SIN vector encoding

CD20 CAR

Lymphodepleting regimen (Cy/Flu)

Cancer stem cell targeting gene-modified T cells

quality control

cell infusion

Cellselection

Finalformulation

Cellactiviation

Cellexpansion

Celltransduction

Automated manufacturing redirected T cells

CliniMACS Prodigy

Priesner C … Koehl U. HGT 2016

BMBF funded multicenter trial: Refractory metastatic Melanoma

cooperation: Miltenyi Biotec, Bergisch GladbachH. Abken, Cologne (Research development) andU. Köhl, MHH, ICT, Hannover (Manufacturing)

manufacturing license: 7/2018

© Fraunhofer IZI

IPC QC

Immuno-selection

SelectedT cells

Formulation &cryopreservation

IMPStorage,

thawing, &application

Activation

day 0

ExpansionCAR

T cells

up to day 10-12

Leuk-apheresis

Mononuclearcells

Patient Cryo-preservation

Thawing

and/or

Trans-duction

day 1

Objective Sample Method / Parameter / MarkerTarget value / Specification

IPC QC: purity / content / identity

starting material, intermediates thawed IMP

CD3, 4, 8, 14, 45, 62L to be defined

IPC QC: purity

intermediates after enrichmentthawed IMP

%T cells of viable mononucleated cells:%(CD3+CD45+) of (CD45+ 7AAD-)

≥80%to be defined

IPCQC: content / identity

starting material, intermediates thawed IMP reference sample

viability of T cells:%7AAD- of (CD3+CD45+)

≥80%≥50%

IPCQC: content / identity

sample of expansion culture (day 6), cultured in parallel (serum free)

transduction frequency:%CAR+ of (CD3+ CD45+ 7AAD-

≥10%

advanced identity / purity

starting material, intermediates thawed IMP

CD45RA, 45RO, 27, 28 / 19, 56 to be defined

potency evaluationintermediates thawed IMP

ELISPOTIFN-γ secretion with malignant cells to be defined

potency evaluationintermediates thawed IMP

Cytotoxicity Assaylysis of malignant target cells

to be defined

Flow

Cyto

metry

(EP 2.7.23

development & validation

Quality Control of CAR-transduced T cellsCytological in-process (IPC), quality (QC), and complementary controls

results

© Fraunhofer IZI

Cell expansionCD62L selected T cells

Final end product at harvesting


transducedT cells

anti-

CAR

CD8

control

results

© Fraunhofer IZI

Cell expansionCD62L selected T cells

Final end product at harvesting


- uniform T cell expansion rate; > 30-foldNo difference cryopreserved versus fresh

- Naive (TN ) and central memory (TCM) T cellsas well as T stem cell like memory cells (TSCM)

transducedT cells

anti-

CAR

CD8

control

CD

3

CD62L

CD

62L

CD45RA CD45RA

CD

45R

O

results

© Fraunhofer IZI

Cellular composition (CD4/CD8 sel.)

OtherWBC

CD20

NK

Monos; Granulos

CD4

CD8

CD3

CD3

CD3

Pure T cells at harvesting

CD

8An

ti-C

AR

Flow Cytometry day12

CD3 CD45

(gate CD3+) (gate CD3+CAR+)

------------------CD4----------------

Apheresis

CD4/CD8selected

cells

Day 12harvesting

Successful transduction efficiency

results

© Fraunhofer IZI

Automation – CAR T cells Clinical CTL019 studyCAR T cellsdevelopment/manufacturing EU

8/2017 (FDA) KymriahTM

New „CAR“ technologies

Proof of concept 2018-2022Sleeping beautytarget antigen: ROR1Helmholtz BerlinFraunhofer IZI/University of Würzburg

„CAR“ NK cells

EU consortium:2018-2022;mono and bi-specificCAR NK cellsNK cell signallingSpeaker: U. Köhl

Bench to bedside and back to the lab

TRUCKs

T cells Redirected for UniversalCytokine Killing

7 Universities

http://www.novartis.de/index.shtml

© Fraunhofer IZI

“CAR” expressing effector cells CAR engineered T cells

- Clinical studies- Manufacturing challenge- in some patients: failure in manufacturing(heavily pre-treated)

„off the shelf“ CAR NK cells

- Clinical NK cell studies- Primary human „CAR“ NK cells- lytic activity- Benefit and side effects

Köhl 2.3.2018

Oberschmidt O, Kloess S and Koehl U. Frontiers Immunology 2017

© Fraunhofer IZI

Donor /Parents

Allogeneic NK-DLI post haplo-SCT (Clin Gov No NCT 01386619) Patients with high risk leukaemia and malignant tumours

NK cell purification(CD3 depl./ CD56 sel.)

IL-2 expansion(1000 U/ml, 10 days)

Leukapheresis GMP

NK cell applicationpatient

GMP

[days post SCT]

haplo-SCT

CD34 sel./ CD3/CD19 depl.

0

2nd NK cell application

+40 +100

3rd NK cell application

NK cell immunotherapy

1st NK cell application

(+3)

Koehl U et al. Blood Cell Mol Dis 2004; Koehl U et al. Klin Päd 2005; Koehl U et al. Front Oncol 2013, Stern M et al. BMT 2013

NK-DLI = NK donor lymphocyte infusion

results

© Fraunhofer IZI

Donor /Parents

Allogeneic NK-DLI post haplo-SCT (Clin Gov No NCT 01386619) Patients with high risk leukaemia and malignant tumours

NK cell purification(CD3 depl./ CD56 sel.)

IL-2 expansion(1000 U/ml, 10 days)

Leukapheresis GMP

NK cell applicationpatient

GMP

[days post SCT]

haplo-SCT

CD34 sel./ CD3/CD19 depl.

0

2nd NK cell application

+40 +100

3rd NK cell application

NK cell immunotherapy

1st NK cell application

(+3)

Koehl U et al. Blood Cell Mol Dis 2004; Koehl U et al. Klin Päd 2005; Koehl U et al. Front Oncol 2013, Stern M et al. BMT 2013

NK-DLI = NK donor lymphocyte infusion

Advantage No severe adverse events in patients Primary aim >10x106 CD56+CD3-/kgBW: 41/49 No graft versus host disease if T cells < 25x103/kg IL-2 stimulation → improved NK cell cytotoxicity

Disadvantage Tumor immune escape mechanism (TIEMs)

Kloess et al. Eur J Immunol 2010; Kloess et al. Oncoimmunol 2015

results

© Fraunhofer IZI

tumor cell MICA

Lyse MMPcleavage

solMICA ↑↑

+

NK

NKpatientNK

NKG2D ↓↓

Kloess S … Koehl U. Eur J Immunol 2010 Kloess S … Koehl U, Oncoimmunol 2016

solMICA dependent tumor immune escape inhibits NK cellsin patients with Neuroblastoma

NK

NK NK

NKNK

NK

NKlysis

IL-2 activated NK cells improve NKG2D mediatedcytotoxicity via scavanging of solMICA in plasma

prior NK cell post NK cell control0

500

1000

1500

20003000

4000

solM

ICA

[pg/

ml]

p

© Fraunhofer IZI

NCT03579927 CD19 Lymphoma Cord blood I/II not yet MD Anderson C.and leukaemia NK cells recruiting Houston, USA

NCT03656705 CCCR Non-small Cell Lung NK92 I recruiting Hospital of Xinxiang Henan, China

CCCR: Chimeric CostimulatoryConverting Receptor

Clinical trials with CAR expressing NK cells

CAR: CD19-CD28-zeta-2A-iCasp9-IL15

© Fraunhofer IZI

Redirected “CAR” NK-92 cell line

UKF-NB-3Neuroblastoma

(NB) tumor

anti-ErbB2/HER2

GD2 Expression

anti-GD2

CAR Expression

even

tsev

ents

fluorescence Esser R et al. J of Cellular and Molecular Medicine 2011

coop. U. Köhl (MHH), W. Wels (FFM), T. Tonn (Dresden)

Schönfeld et al. Molecular Therapy 2014

results

© Fraunhofer IZI

Chimeric Antigen Receptor Vector Designfor primary human NK cells

Endodomain: FMC63 → CD19 Endodomain: CD28 + 4-1BB(CD137) +CD3 ζ

Codon-optimization: removal of cryptic splice sites, polyadenlyationsignals and other inhibitory sequences

→ CD19 binding leads to signal transduction→ Enhanced cytotoxicity

coop.: A. Schambach, MHH

A. Schambach

© Fraunhofer IZI

CAR expressing NK cells redirected against CD19

dNK cellsvs. BV173

MOI1

dNK cells : CD19+ BV173 incubation time [h]; E:T ratio: 5:1

CD19-CAR-dNK cellsvs. BV173

CD19-CAR-dNK cellsvs. BV173+CD19mAB

blocking

Suerth J et al. J Mol Med August 2015

Alpha SIN vector

FSC-H

EGFP

Mock alpha

Transduction of mature primary human dNK cells feasible

EGFP

[%]

MOI

results

© Fraunhofer IZI

Köhl 27.03. 2017

Secretions of cytokines and pro-apoptotic molecules by CAR NK cells

anti-inflammatory:IL-4

IL-10

pro-inflammatory:IL-6

IL-17AIFNγTNFα

pro-apoptotic:GrAGrB

PerforinGranulysin

CD56brightCD16dim&neg(immune regulatory) CD56

dimCD16pos(cytotoxic)

E/T 1:1 5:1

++ 0+ +

++ +++ ++ +

++ ++

+ 00 0- -0 +

E/T1:1 5:1

+ ++ +

+ ++ -- -+ +

++ + ++ ++ + +0 ++

results

© Fraunhofer IZI

Primary CAR expressing NK cells

redirected against AML cell lines and

patients own leukemic cells

123+ AML

Coop.: M. Morgan, A. Schambach, M. Heuser

© Fraunhofer IZI

IL-2 activated NK cellsagainst KG1a

MOI3

NK cells : CD123+ KG1a incubation time [h]; E:T ratio: 10:1

CD123-CAR-NK cellsagainst KG1a

CD123-CAR-NK cellsagainst KG1a + CD123 mAB

blocking

0 .1 5 1 8 2 4 0 .1 5 1 8 2 4 0 .1 5 1 8 2 40

5 0

1 0 0

1 5 0

2 0 0

2 5 0

3 0 0

CD

12

3+ le

uke

mia

bla

sts

[ce

lls/µ

l]

CD56 APC CD56 APC CD56 APC

CD

34 P

C7

CD

34 P

C7

CD

34 P

C7

Coop.: A. Schambach, MHH

CAR expressing NK cells redirected against CD123+

Kloess et al. Human Gene Therapy 2017

results

© Fraunhofer IZI

CAR NK cells against patient´s CD123+AML

5 2 4 5 2 4 5 2 4 5 2 40

2 5

5 0

7 5

1 0 0

tim e [h ]

Cyt

oto

xici

ty [

%]

Mock EGFP CD123 CAR/ CD123 CAR/EGFP EGFP + anti-

CD123

CAR-NK cells vs.

patient´s AML(E/T: 1:1)

MOI1

Coop.: M. Heuser, A. Schambach MHH

5 2 4 5 2 4 5 2 40

1 0

2 0

2 5

5 0

7 5

1 0 0

tim e [h ]

Cyt

oto

xici

ty [

%]

CAR-NK cells vs. HLMVEC (E/T: 1:1)

Mock EGFP CD123CAR/EGFP

Side effects

Cytotoxicity

Kloess et al. Human Gene Therapy 2017

S. Kloess

results

CD123CAR expressing NK cells and EGFP+ mock NK cellsaginst CD123 positive KG1α targets

Klöß 27.06.2017

CD123+KG1α cell proliferation dye: eFluor®450, anti-CD34-PE

anti-CD123-CAR NK cells EGFP+

NK:KG1 E:T ratio: 5:1; MOI1

anti-CD16-APC, EGFP+ NK cells

© Fraunhofer IZI

Clinical scale – CAR expressing NK cells

Product-development

DevelopmentQuality control

Release of product

UpscalingValidation

„Off the shelf product“ Advanced Therapy Medicinal Product

GMP-compliant protocol

SOP=standard operation protocol CMC=chemical manufacturing and control IMPD=investigational medicinal product dossier

results

© Fraunhofer IZI

Clinical scale – CAR expressing NK cells

Product-development

DevelopmentQuality control

Release of product

UpscalingValidation

„Off the shelf product“ Advanced Therapy Medicinal Product

GMP-compliant protocol

SOP=standard operation protocol CMC=chemical manufacturing and control IMPD=investigational medicinal product dossier

0 2 4 6 8 1 0 1 2 1 40 .0

0 .5

1 .0

1 .5

2 0

4 0

6 0

8 0

1 0 0

d N K c e ll e x p a n s io n

D a y s in c u ltu re

x-fo

ld e

xpa

nsi

on

IL -2

fe e d e r c e lls + IL -2

fe e d e r c e lls + IL -2 1 /-2

cell expansion

results

© Fraunhofer IZI

CAR expressing effector cells conclusionCAR T cells: Successful clinical CAR T cells studies (385 documented world wide)

Our data about automated manufacturing of CAR expressing T cells givesrise for harmonized protocols in future clinical studies

Manufacturing failure of autologous CAR T cells needs complementary concepts

Primary human CAR NK cells: Patients can receive allogeneic haploidentical or „third party NK cells“ without

severe side effects → good candidates for „off the shelf CAR products“

CAR NK cells (alpha retroviral SIN vectors) reached a nearly complete elimination of CD19+ and CD123+ leukemic cells after 48 h

Improvement in future studies: CAR expressing cells and checkpoint inhibitors → combination CAR effector cells with transient cytokine secretion

© Fraunhofer IZI

Inst. Cellular Therap., MHH Hannover, DR. EsserS. KlössW. GlienkeO. Oberschmidt

L. ArsenievK. AleksandrovaC. PriesnerJ. Leise

Internal Medicine, Würzburg, DM HudecekH. Einsele

[email protected]@mh-hannover.de

www.mh-hannover.de/zelltherapeutika.htmlwww.izi.fraunhofer.de

Tumorimmunology, RegensburgH. Abken

Kantons-Spital Basel, CHJ. Passweg M. Stern C. Kalberer

A. Schambach M. Morgan H. Büning T. Moritz

Experimental Haematology, MHH, D

Haematol. /Oncol./ SCT, MHH, D

E. Seifried C. Seidl T. TonnBSD Hessen/BW und BSD Ost, D

A. Ganser M. Heuser M. Eder C. Könecke

Fraunhofer Cell. Therapy IZI, Leipzig, DF. EmmrichG. SchmiedeknechtK. KebbelJ. LehmannA. Bochmann-SeidelS. Mitzner

U. DemuthS. UlbertF. HornT. GrunwaldT. TradlerS. Fricke

Clinic. Immunol., University Leipzig, DU. Sack A. Boldt

W. WelsGeorg Speyer House Frankfurt, D

C. Kratz M Sauer B Maecker-KolhoffPediatric Hematol/ Oncol., MHH, D

T. Klingebiel D. Schwabe P. Bader S. HüneckePediatric Hematol/ Oncol., Frankfurt, D

R. Blasczyk L. Goudeva B. Eiz-VesperTransfusion Medicine, MHH, D

.

C. RössigPediatric Hematol/ Oncol., Münster, D

http://www.bmbf.de/http://www.miltenyibiotec.com/

Diagnostic - devicescell-based therapies

GMP

Havard Medical School * BostonGene Therapy

Internationalpartners

72 Institutes> 25.000 staff members

TechnologiesAutomation

© Fraunhofer IZI

Harmonisation

Network for individualised stratified medicineusing cell-based

therapies

…. and thanks for listening

Automatisierung von CAR EffektorzellenFoliennummer 2Foliennummer 3Foliennummer 4Foliennummer 5Foliennummer 6Foliennummer 7Foliennummer 8Foliennummer 9CTL019 pediatric r/r ALL – ELIANA �”Event-free” and “overall survival”Foliennummer 11Foliennummer 12Foliennummer 13ENGINEERING EFFECTIVITYFoliennummer 15Automated manufacturing of CAR T cellsFoliennummer 17Foliennummer 18Foliennummer 19Final end product at harvestingFinal end product at harvestingCellular composition (CD4/CD8 sel.)Bench to bedside and back to the labFoliennummer 24Foliennummer 25Foliennummer 26Foliennummer 27Foliennummer 28Foliennummer 29Foliennummer 30Foliennummer 31Foliennummer 32Foliennummer 33Foliennummer 34Foliennummer 35Foliennummer 36Foliennummer 37Foliennummer 38Foliennummer 39Foliennummer 40Foliennummer 41Foliennummer 42Foliennummer 43

Automatisierung von CAR Effektorzellen · * A conflict of interestis any situation in which a...

Documents

Transcript of Automatisierung von CAR Effektorzellen · * A conflict of interestis any situation in which a...