HAL Id: inserm-00484505
https://www.hal.inserm.fr/inserm-00484505
Submitted on 18 May 2010HAL is a multi-disciplinary open access
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Caroline Aspord, Julie Charles, Marie-Thérèse Leccia, David Laurin,
Marie-Jeanne Richard, Laurence Chaperot, Joël Plumas
To cite this version:
Caroline Aspord, Julie Charles, Marie-Thérèse Leccia, David Laurin, Marie-Jeanne Richard, et al.. A novel cancer vaccine strategy based on HLA-A*0201 matched allogeneic plasmacytoid dendritic cells.. PLoS ONE, Public Library of Science, 2010, 5 (5), pp.e10458. �10.1371/journal.pone.0010458�. �inserm-00484505�
A
B
tumor antigen mRNA expression
cell line -+low -A375 + + + + COLO829 + + + + Mel89 + + + + Me275 MAGE-3 TYR GP100 MelA 100 101 102 103 104 HLA-A2 FITC 100 101 102 103 104 HLA-A2 FITC 100 101 102 103 104 HLA-A2 FITC 100 101 102 103 104 HLA-A2 FITC 100 101 102 103 104 MelA FITC 100 101 102 103 104 MelA FITC M1 100 101 102 103 104 MelA FITC M1 100 101 102 103 104 MelA FITC M1 HLA-A2 MelA Me275 (HLA-A2+ MelA+) Mel89 (HLA-A2+MelA+) COLO829 (HLA-A2-MelA+) A375 (HLA-A2+MelA-)
% t e tr a m e r+ C D 8 T c e lls Flu M1 d0 d7 0.01 0.1 1 10 100 A B CD8 d7 d0 Flu M1 tetramer 19% 0.04% C D % t e tr a m e r+ C D 8 T c e lls CMVpp65 d0 d7 0.01 0.1 1 10 100 CMVpp65 tetramer CD8 d7 d0 25% 0.14%
0 20 40 60 80 100 60:1 30:1 15:1 7.5:1 E:T ratio % k ill in g T2 Flu T2 MelA K562
Flu specific T cells
C
Flu specific T cells T2 MelA T2 Flu IFNγ CD107 Flu tetramer 31% 1.3% 75.5% 11.9% restimulation : tetramer+ CD8 T cells tetramer-CD8 T cells CD4 T cells % o f IF N γ + T c e lls PBMC + GEN Flu - d8 restimulation : T2 -GEN MelA Flu MelA Flu 0 20 40 60 D C D 1 0 7 + T c e lls restimulation : PBMC + GEN Flu - d8 tetramer+ CD8 T cells tetramer-CD8 T cells CD4 T cells 0 20 40 60 80 T2 GEN -MelA Flu MelA Flu
A
B
response to MelA vaccination
d0 d10 d14 d21 d32 0.001 0.01 0.1 1 10 0.001 0.01 0.1 1 10 d0 d10 d14 d21 d32 0.001 0.01 0.1 1 10 d0 d10 d14 d21 d32 0.001 0.01 0.1 1 10 d0 d10 d14 d21 d32 blood lavage spleen MLN % t e tr a m e r C D 8 T c e lls
response to Flu vaccination
blood lavage spleen MLN % t e tr a m e r C D 8 T c e lls 0.01 0.1 1 10 d0 d7 d14 d21 d32 0.01 0.1 1 10 0.01 0.1 1 10 0.01 0.1 1 10 d0 d7 d14 d21 d32 d0 d7 d14 d21 d32 d0 d7 d14 d21 d32
PBMC patient #4 TYR tetramer CD8 d0 d7 d14 85% 43% 1.8%
100 101 102 103 104 CD40 PE 100 101 102 103 104 HLA-A2 FITC 100 101 102 103 104 CD86 PE 100 101 102 103 104 CD80 FITC
CD80
CD86
HLA-A2
CD40
30Gy irradiation
% t e tr a m e r+ C D 8 T c e lls 0 1 2 3 4 5 anti-IFNαβ Abs control Abs
1 0.1 0.01 0.001 0.000 1 0 20 40 60 80 100 % o f m a x im u m l y s is (E :T r a ti o 3 0 :1 ) pDC line mDC
peptide concentration on T2 cells (µM) 0 20 40 60 80 100 T2 loaded with irrelevant peptide unloaded T2
