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 / Martin Hildebrandt

2. 3
Aim: Translation into Clinic
GLP
GCP
GMP
Industry
Z3
legal and
regulatory aspects
Introduction
§

3. 3
Road Map
GMP Process
GCP Phase I Study
Laboratory Protocols
TCR/CAR Selection
GMP Manufacturing
Clinical Setting
Risk Assessment
Safety
Efficacy Testing
SOP / Validation
Manufacturing License
Protocol/Ethical Vote
Funding Application
Clinical Study
Introduction

4. 3
Accomplishments (Berlin – Munich)
Milestone 1
01-2012
Teams and collaboration tools
Milestone 2
03-2012
Definition of target product profiles (TPP)
Milestone 3
06-2012
Project evaluation and priorization
Milestone 4
08-2012
Description of manufacturing process
Milestone 5
12-2012
Phase I Study protocol
Milestone 6
02-2013
PEI Advice (positive)
Milestone 7
08-2013
Master Cell Banks
Recent work
HMMR

5. 3
Collaboration in process development
HBV-CAR
against HCC
Exchange of documents
Contract management
Risk assessment
Quality controls
Vendor qualification
Joint scientific advice
Shared audits
Validation
Joint appointments
Successful translation
Work program
MAGE-A1 TCR
against MM

6. Example: Trial I – TCR transduced T cells
Multiple Myeloma
MAGE-A1+
TCR against
MAGE-A1
Production of
TCR transduced
T cells
Application of
TCR transduced
T cells
Disease
TCR
Production
Therapy
not curable with
conventional
therapies
no expression of
MAGE-A1 on healthy
tissues
ATMP (GTMP)
production
Phase I
tumor susceptible
towards T cell
mediated immunity
high effectiveness in
vitro and in mouse
model
autologous cells
(HLA identical)
12 patients
refractory or high risk
disease
Procedural advisory board: Dolores Schendel (preclinical), Hans-Jochem Kolb (clinical)

7. 3
Process development (Berlin – Munich)
TCR
CAR
Milestone 1
06-2013 11-2013
Milestone 2
06-2014
Definition of TPP and QC
07-2014
Phase I protocol and safety board
Milestone 3
09-2014
08-2014
Validation of GMP Process
(EUFETS, SCF, TUMCells)
Milestone 4
05-2015
09-2015
IMPD, Manufacturing license
Milestone 5
09-2015 01-2016
Ethic vote, EudraCT Number
Milestone 6
10-2015
02-2016
Clinical trial authorization
Start of clinial trial
Work program

8. Collaboration within the SFB TR36
A3, A4, A11, B8, B9
Development of production
processes
Development of clinical protocols
T1
A2
Development of TCRs for
clinical use:
MAGE-1, NY-ESO
Novel epitopes
Z1
Z3
A13, A14
Pre-clinical safety testing
GMP upscaling
Regulatory support