Christine MENETRIER-CAUX - Cancéropôle Lyon Auvergne Rhône

SOUS L'ÉGIDE DE LA FONDATION BULLUKIAN
AC C É L É R A T E U R D ’A V A N C É E S
CANCÉROPÔLE LYON AUVERGNE RHÔNE-ALPES
LYMPHOS’1 Project
Plateforme
d’Innovation
en Immuno-monitoring
et Immunothérapie
PI3
Plateforme
d’Innovation
en Immuno-monitoring
et Immunothérapie
PI3

SOUS L'ÉGIDE DE LA FONDATION BULLUKIAN
LYMPHOS’1 Project Identity Card
2 partners : Centre Léon Bérard / Centre de Recherche en Cancérologie de Lyon
(CRCL) & ImmunID Technologies
2 localizations : Lyon / Grenoble
Project Duration: 4 years (2008-2012)
Global Budget : 853 k€ (50% for the academic partner financed by CLARA/Rhône)
Proof of concept: Demonstrate the clinical interest to detect
systemic immune dysfunctions in metastatic breast carcinoma
Objective:Validate a prognostic test to characterize at risk
patients that will benefit from innovative therapeutics
Plateforme
d’Innovation
en Immuno-monitoring
et Immunothérapie
PI
3Plateforme
d’Innovation
en Immuno-monitoring
et Immunothérapie
PI
3

SOUS L'ÉGIDE DE LA FONDATION BULLUKIAN
•20-30% patients with metastatic solid tumors show a lymphopenia associated
with complications:
•Febrile neutropenia (Blay JY et al. JCO 1996 92:405-10)
•Grade IV anemia and thrombocytopenia (Ray-Coquard I. et al. JCO 1999 17:2840-6)
•Increased risk of Early Death (48%) (Ray-Coquard I. et al. Br J Cancer 2001 85:816-22)
SCIENTIFIC BACKGROUND
DATE NOM DE LA PRÉSENTATION (INSERTION - EN-TÊTE ET PIED DE PAGE) 3
lymphocytes (/µL)
>1000/µL
<1000/µL
Metastatic Breast Carcinoma (n= 290)
Months
100806040200
Overall survival (%)
100
80
60
40
20
0
Log Rank test =21.5, p<0.01
Soft tissue Sarcoma (n=193)
Years
012 3 4 5 6 78
0
10
20
30
40
50
60
70
80
90
100 Log Rank test: p=0.0057
lymphocytes (/µL)
>1000/µL
<1000/µL
Overall survival (%)
•Lymphopenia detected before chemotherapy is an independent pronostic
factor for overall survival in metastatic solid tumors (Borg C et al. Cancer 2004
101:2675-80; Ray-Coquard I. et al Cancer Res 2009 69:5383-91)
Plateforme
d’Innovation
en Immuno-monitoring
et Immunothérapie
PI
3
Plateforme
d’Innovation
en Immuno-monitoring
et Immunothérapie
PI
3

SOUS L'ÉGIDE DE LA FONDATION BULLUKIAN
Flow
Cytometry
(V)
Spectratyping &
Sequencing
(CDR3)
(V-J)
Combinatorial diversity : V x (D) x J
Jonction diversity: CDR3
Matching diversity : TCRa x TCRb
Somatic hypermutations
Identification of V-J rearrangements at the genomic level
Stability of samples
Avoid bias due to transcriptional regulation (1 cell = 1 rearrangement)
PCR multi-N-plex
gDNA
V-Ja
Rearrangement
J genes AC
Splicing
Vn -
Ji A
C
Vn - Ji
Env. 10Kb
V genes
A
C
Example : TRAD Locus
ImmunID Technology to assess TCR diversity
V
Hz
J

SOUS L'ÉGIDE DE LA FONDATION BULLUKIAN
TCR repertoire diversity is altered in metastatic breast cancer
patients and has an added value to lymphopenia status
Lymphopenic Patients Non Lymphopenic
Patients
Divpenia<1st tertile