Онколитические вирусы. Доставка опухолеспецифичных антигенов антигенпрезентирующим клеткам

План
Иммунный ответ на вирусную инфекцию
Компоненты противоопухолевого иммунитета
Стратегии создания онколитических вирусов
Immune checkpoints

https://doi.org/10.1038/nrd4663

https://doi.org/10.1038/nrd4663

Dendritic cells
Classical
Non-classical
CD8+ (lymphoid organs)
CD103+ (intestinal mucosa)
CD11b+ (lymphoid organs)
Langerhans cells
Monocyte-derived DC Plasmacytoid DC, CD1C+
(IRF7; IL-12, IL-6)

VSV (Vesicular Stomatitis Virus)
Family: Rhabdoviridae
Group: (-)ssRNA
https://doi.org/10.1016/j.molmed.2004.03.003

Adenoviruses
Family: Adenoviridae
Group: dsDNA
Cell receptors: CD46, CAR
(coxsackievirus adenovirus
receptor)
E1A
Rb protein
E2F (tf)
Cell cycle (S-phase)
E1B
p53

PeptiCRAd
(peptide-coated conditionally replicating adenovirus)
https://doi.org/10.1080/2162402X.2015.1105429

Measles virus
Family: Paramyxoviridae
Group: (-)ssRNA
https://doi.org/10.1080/2162402X.2016.1261240

Flow cytometry assay
https://doi.org/10.1080/2162402X.2016.1261240

Herpes simplex virus
Family: Alphaherpesvirus
Group: dsDNA
Herpes virus entry mediator
T-VEC (Talimogen laherparepvec)

https://doi.org/10.1007/s40257-016-0238-9

Vaccinia virus
Family: poxvirus
Group: dsDNA (190 kb)
Intracellular pattern recognition receptor DNA-dependent activator of IFN-regulatory factors (DAI)
Deletions: thymidine kinase gene
vaccinia growth factor
https://doi.org/10.1038/mto.2016.2

viRNA
Vaccinia virus + lipofectamine + mRNA (ovalbumin)
Naïve splenocytes
Flow cytometry assay

Poliovirus
Family: Picornaviridae
Group: ssRNA
CD155 in glioma cells
Exchange of the poliovirus internal ribosomal entry site with its counterpart from human Rhinovirus type 2 resulted in attenuation of neurovirulence in primates
https://doi.org/10.18632/oncotarget.12975

PVSRIPO in human breast and prostate cancer xenograft models
SUM 149 breast cancer cell line
DU145 prostate cancer cell line
https://doi.org/10.18632/oncotarget.12975

Cowpea mosaic virus
Family: Secoviridae
Group: (+)ssRNA

Co-inhibitory pathways

Cytotoxic T-lymphocyte antigen 4 (CTLA-4)
Homolog of CD28 (binds CD80 and CD86)
Multiorgan inflammation develops in CTLA-4 knockout mice
Ipilimumab
Tremelimumab

Programmed death 1 (PD-1)
The level of PD-1 is high when T-cells are repetitively stimulated
Expressed on NKs, B-cells, Tregs, macrophages
Has 2 ligands: PDL-1 and PDL-2 (on APCs, tumor cells)
Nivolumab
Pembrolimumab
10.1146/annurev-immunol-032414-112049