A novel cancer vaccine strategy based on HLA-A*0201 matched allogeneic plasmacytoid dendritic cells.

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HAL Id: inserm-00484505

https://www.hal.inserm.fr/inserm-00484505

Submitted on 18 May 2010

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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�

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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-₎

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% 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%

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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

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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

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PBMC patient #4 TYR tetramer CD8 d0 d7 d14 85% 43% 1.8%

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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

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% 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

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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