Graham Taylor (University of Birmingham, United Kingdom)
“The NPC Immunotherapy Landscape”
Broad CD8+ and CD4+ T cell responses to vaccination in ex Vito ELIspot immune assays
– weal pre-existing EBVNA1 and LMPO2 T-cell
– Vaccination simulates multiple CD8+ and CD4+ T cell responses within an individual; lpatuens
– Anti-tumor T cell responses before vaccination
– 95% T celll go to tissues, 5% T cell in the blood (>)
– Cultured T cell assay
– — otauent cells in 96U plate culture 10-14 days
– Responses after chmoradiotherapy , below limit of detection ion ex Vito assays can amplify after vaccination
– UK phase 1Blocker trial, 80 year kid oatuebntm remission ., Signle diodes 5x 10^8
Possible epitope spreading to non-target antigens (HK Phase II Trial, patten
– no target antigen BARF1
So far, just IFNG as a read out, this is only one dimension f data —> MHC-tetramers (MHC + 3 antigens) will add additional readout
EBNA1 CD4+tetramer
Vaccination increases expression of T-cell himning receptor implicated in T-cell homing to NPC (CXCR3 expression by CD4+ T-cells strongly suggests Th1 phenotype)
Tree:
T-reg are CD25hi, CD127lo.
– EBNA1-specific CD4 T-cells are CD25lo CD127hi (thus these are not T-reg, but are Th1 cells)
CD127+ve T cells can respond to IL7 and are thought to be ling-lived nmmeory T -cells
The cancer immunity cycle
– Imunity 2013
– Nature 2011
– NEJM 201
[New insight in to NPC immune landscape]
– several if these changes have been seen in previous studies (decreased CD4, increased NK, increased T-reg
– heat amp of cell sub
Low CD4:CD8 = poor unable fybctun due to ummunoscencece
and High% T-reg are proportion of CF4 T-cell pool
Low @ T-reg as proportion of lymphocytes
High @ MDSCs
Conclusion : a sub population of NPC patients have a multiple immune defects (low CD4: CD8)
Future work-higher dimensional analysis of NPC immunity
– 35 marker CyTOF panel, ready for use
[Characterisaiotn of target cell lines in preparation for in vitro assays with EBNA1 and LMP2-specific T cell clines
NP46 normal
C17 (NPC
LCL (B cell Line)
T-cell therapy
IFNG makes NP460 NP460 and C17 increase MHC II
T-cells undergoing Ca2+ Flux (activation) with loading peptides
Time-lapsed microscope
A recent Immunity paper about EBV vaccination
Mathematical modeling of EBV transmission to identify essential qualities needed for an effective prophylactics vaccnine and vaccination strategy [yet, we need more dimensions of data]