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Transregional Collaborative Research Centre TR36”Principles and Applications of Adoptive T Cell Therapy“
Platform for clinical application of genetically engineered T cells with
defined specificity
Lutz Uharek / Hans-Jochem Kolb
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Bringing a cellular product into the clinic
Legal andregulatory aspects
GLPGLP
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GCP
GMP
Introduction
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Production Steps
GMPout
sourced
Cloning of Ag-specific T cells
Determination of TCR specificityAmplification of TCR genes
Construction of TCR-retrovirus vector
Production of TCR-retrovirus particles
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22
Introduction
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Production steps and application
GCP
GMPGCP
Transduction of patients‘ T cells
Functional characterisationof TCR-redirected T cells
Enrichment and expansionof TCR-redirected T cells
Patient enrollmentin phase I study
Infusion of TCR-redirected T cells
Monitoring
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Introduction
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Aim
Define optimal clinical setting for use of antigen-specific 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
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Clinical Phase II Trials
Results
Example 1: Donor T cells in AML
DLI
no DLI
FLAMSA-Study Group 2006
Example 2: CD56+ NK cells in AML
N=46
N=26
0 500 1000 1500 2000Days post transplantation
0 1000 2000 3000Days post transplantation
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Schedule
GMP Manufacturing
Risk Assessment
Efficacy Testing
TCR Selection
Clinical Setting
Safety
Manufacturing License
Laboratory Protocols
Protocol/Ethical Vote
Funding Application Clinical Study
SOP / Validation
GCP Phase I StudyGMP Process
Standar ds / M
o dules
Deliverable I
Deliverable II
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Work programme
Collaboration within the SFB TR36
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A1, A4, B8, B9Generation of T cells
for clinical trials
A13Evaluation and monitoring
of TCR efficacy
Z1, Z2T cell receptor engineering
Clinical monitoring
A2, B1Mouse models for
safety testing
B2, Z1 Transfer of laboratory protocols
in GMP