1. Transregional Collaborative Research Centre TR36
”Principles and Applications of Adoptive T Cell Therapy“
Z3
Platform for clinical application of
genetically engineered T cells with
defined specificity
Lutz Uharek / Hans-Jochem Kolb

2. 3
Bringing a cellular product into the clinic
GLP
GLP
GCP
GMP
Z3
Legal and
regulatory aspects
Introduction

3. 3
Production Steps
Cloning of Ag-specific T cells
1
1
Determination of TCR specificity
Amplification of TCR genes
2
2
Construction of
TCR-retrovirus vector
GMP
out
sourced
Production of
TCR-retrovirus particles
Introduction

4. 3
Production steps and application
3
3
Transduction of patients‘
T cells
Enrichment and expansion
of TCR-redirected T cells
GMP
GCP
Functional characterisation
of TCR-redirected T cells
Patient enrollment
in phase I study
4
4
Infusion of TCRredirected T cells
GCP
Monitoring
Introduction

5. 3
Aim
Define optimal clinical setting for use of antigenspecific T cells in antiviral and tumour therapy
Create a modular protocol platform for GMP compliant
production of TCR engineered T cells
Provide a phase I protocol for adoptive transfer of
T cells carrying a genetically modified TCR
Basis:
Substantial experience in the development of clinical trials with
donor lymphocyte transfusions
Successfull development of different GMP conform manufacturing
processes for various cellular products
Work programme

6. 3
Clinical Phase II Trials
Example 1:
Donor T cells in AML
Example 2:
CD56+ NK cells in AML
DLI
N=46
N=26
no DLI
0
0
500
1000
1500
Days post transplantation
2000
FLAMSA-Study Group 2006
Results
1000
2000
Days post transplantation
3000

7. GMP Process
GCP Phase I Study
Laboratory Protocols
TCR Selection
GMP Manufacturing
Standards / Modules
3
Schedule
Clinical Setting
Risk Assessment
Safety
!
Efficacy Testing
SOP / Validation
Manufacturing License
Deliverable I
Protocol/Ethical Vote
Deliverable II
Funding Application
Clinical Study
Work programme

8. Collaboration within the SFB TR36
A1, A4, B8, B9
Generation of T cells
for clinical trials
B2, Z1
Transfer of laboratory protocols
in GMP
A2, B1
Mouse models for
safety testing
Z3
Z1, Z2
T cell receptor engineering
Clinical monitoring
A13
Evaluation and monitoring
of TCR efficacy