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Christophe MasPhD, CSO
A novel 3D human tissue culture model
for in vitro lung cancer research
Lung cancer
Colon cancer
Mesothelioma
Nasal cavity cancer
2 Lush Prize – London Nov2015
Human in vitro tissue modelsfor cancer research
Geneva, Switzerland
Lung cancer
3Lush Prize – London Nov2015
Source : IARC, 2012
>1 million deaths
4
Lung cancer: clinical management
Broad chemotherapies
>1 milliondeaths
► cisplatin
► paclitaxel
► docetaxel
► pemetrexed
Second lineTargeted therapies
>1 milliondeaths
► erlotinib► gefitinib► afatinib
► crizotinib► ceritinib
► ramicirumab► bevacizumab
Cuaron et al. Front. Oncol. 2013; 2:208.
baseline 4 months 9 months
pemetrexed + bevacizumab (PET scan)
recurrence
First line
Lush Prize – London Nov2015
Tumor cell line xenograft
mut*
Lung adenocarcinomas ( K-rasG12D p53f/+ )
SCLC (Rb1f/f ; p53f/f)
Genetically Engineered Mouse (GEMs)
Current preclinical models
Patient Derived Xenograft (PDX)
5Lush Prize – London Nov2015
>1.5 million
► Failure rate for new drugs > 85% !
100% human in vitro 3-Dimensionnal accessible
A new model for lung cancer research
Goblet CellsCiliated
Human Fibroblasts
Basal cells
Tumor
6Lush Prize – London Nov2015
Process overview
7Lush Prize – London Nov2015
1 mm
B
*
100 µm
A
OncoCilAir™
Histology and confocal imaging
8Lush Prize – London Nov2015
RAF
EGF
EGFReceptor TK
GRB2
ERK
SOS
Cell proliferationdecreased
KRAS
nucleus
KRAS activated in 30% of lung adenocarcinoma
erlotinib
Efficacy study of the MEK inhibitors Selumetinib and Trametinib
selumetinib / trametinib
MEK1/2inhibitors
MEK
11Lush Prize – London Nov2015
erlotinib selumetinib trametinib
day
0da
y 9
DMSO
day
20
Efficacy study of the MEK inhibitors Selumetinib and Trametinib
12Lush Prize – London Nov2015
treatment wash
days
selumetinib trametinib erlotinib
selumetinib
trametinib
13Lush Prize – London Nov2015
Lung adenocarcinoma stratification
Lung CancerNSCLC
adenocarcinomas
KRAS
PTEN
EGFR
30%
15%
3%
ALKEML4
HER2
AKT
MET
DDR2
MEK
BRAF
FGFR1ROS1
NRAS
PIK3CA
RET1
Panel of OncoCilAirTM
1
2%
4%
1
1
1
2%
1
1
2%
4%
50%
1
14Lush Prize – London Nov2015
Bonchial NormalPrimary Human Cells
GFP+ reporter
combination, amplification & seeding
OncoCilAirTMTranswell
insert
PatientPrimary Tumor Cells
Patient derived OncoCilAir™
15Lush Prize – London Nov2015
PDOCA_023 PDOCA_023_5x
Squamous cell carcinoma Day10
Patient derived OncoCilAir™
16Lush Prize – London Nov2015
• Healthy airway epithelium• Tumour nodules Concurrent testing of efficacy AND toxicity
• Lifetime > 3 months Chronic exposure Test of recurrence Development of resistance
• Air-liquid interface Aerosol therapies Systemic treatment
Mas et al. J Biotechnol. 2015 ;205:111-9.
“ Antitumour efficacy of the selumetinib and trametinib MEK inhibitors in a combined human airway–tumour–stroma lung cancer model ”
17Lush Prize – London Nov2015
OncoCilAir : an innovative in vitro lung cancer model
Side-toxicity evaluation
Trans EpithelialElectrical Resistance
CytotoxicityLDH
19Lush Prize – London Nov2015
