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Immunology 2018
J u l y 0 5 - 0 7 , 2 0 1 8
V i e n n a , A u s t r i a
Page 113
Journal of Clinical Immunology and Allergy
ISSN 2471-304X
1 5
t h
I n t e r n a t i o n a l C o n f e r e n c e o n
Immunology
O
ncolytic viruses (OVs) are among the most powerful approaches in cancer immunotherapy. OVs not only cause cancer cell
lysis but more importantly, their infection in tumors induces anti-tumor immune response from the host, resulting in lasting
anti-tumor immunity. It has been recognized that anti-tumor immune response requires multiple immune regulatory factors that
act synergistically and tumor microenvironment is critical for tumor to grow. Herpes simplex virus type-1 (HSV-1) has been
approved by FDA as an oncolytic viral drug to treat melanoma. One advantage of HSV-1 is its large genomic capacity for carrying
multiple exogenous genes. A HSV-1 oncolytic viral vector (VG161) was constructed to simultaneously express IL12, IL15 with its
receptor alpha unit and a PDL-1 blocking peptide. Anti-tumor activity of VG161 was tested in both immune competent mice (CT26
and A20 tumor models) and nude mice for human tumor models (LNCaP and U87). Since CT26 and A20 are poorly permissive
for HSV-1 replication, the mouse tumor models were able to demonstrate the anti-tumor immune response induced by VG161
while oncolytic activity of VG161 was demonstrated in LNCaP and U87 models since the immune system is compromised in
those models. VG161 completely inhibited tumors in all the models tested and the animals survived tumor-free for many months
till sacrificed. VG161 induced tumor oncolysis in both LNCaP and U87 tumors. In the CT26 model, animals were protected from
the second challenging with CT26 cells following previous virally induced tumor regression. Furthermore, in a A20 double tumor
model, intratumoral injection into the tumor on one side caused tumor regression on both sides. Transcriptom analysis showed
significant change in tumor microenvironment. Finally, tumor specific memory T-cells were evident in the treated animals. The
anti-tumor immune response by VG161 was significantly stronger than similar viruses that did not express any immune stimulating
gene or only express GM-CSF. These results showed that intratumorally expressed multiple immune regulatory factors by an
oncolytic virus may significantly change the tumor immune microenvironment to enhance efficacy of the oncolytic virus
w.jia@ubc.caSynergistic activation of anti-tumor immunity by
an armed oncolytic virus VG161
W Jia
1, 2
, J Ding
1
, D Choujenko
1
, Y Murad
1
, E Lee
1
, G Liu
1, 2
and L Bu
1, 2
1
Virogin Biotech Ltd, Canada
2
University of British Columbia, Canada
Insights Allergy Asthma Bronchitis 2018, Volume: 4
DOI: 10.21767/2471-304X-C1-003