Delta-24-RGD oncolytic adenovirus elicits anti-glioma immunity in an immunocompetent mouse model.
BACKGROUND
Emerging evidence suggests anti-cancer immunity is involved in the therapeutic effect induced by oncolytic viruses. Here we investigate the effect of Delta-24-RGD oncolytic adenovirus on innate and adaptive anti-glioma immunity.


METHODS
Mouse GL261-glioma model was set up in immunocompetent C57BL/6 mouse for Delta-24-RGD treatment. The changes of the immune cell populations were analyzed by immunohistochemistry and flow cytometry. The anti-glioma immunity was evaluated with functional study of the splenocytes isolated from the mice. The efficacy of the virotherapy was assessed with animal survival analysis. The direct effect of the virus on the tumor-associated antigen presentation to CD8+ T cells was analyzed with an in vitro ovalbumin (OVA) modeling system.


RESULTS
Delta-24-RGD induced cytotoxic effect in mouse glioma cells. Viral treatment in GL261-glioma bearing mice caused infiltration of innate and adaptive immune cells, instigating a Th1 immunity at the tumor site which resulted in specific anti-glioma immunity, shrunken tumor and prolonged animal survival. Importantly, viral infection and IFNγ increased the presentation of OVA antigen in OVA-expressing cells to CD8+ T-cell hybridoma B3Z cells, which is blocked by brefeldin A and proteasome inhibitors, indicating the activity is through the biosynthesis and proteasome pathway.


CONCLUSIONS
Our results demonstrate that Delta-24-RGD induces anti-glioma immunity and offers the first evidence that viral infection directly enhances presentation of tumor-associated antigens to immune cells.
Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Hong
H
Jiang
Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Karen
K
Clise-Dwyer
Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Kathryn E
KE
Ruisaard
Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Xuejun
X
Fan
Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Weihua
W
Tian
Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Joy
J
Gumin
Department of Neurosurgery, Erasmus MC, Rotterdam, The Netherlands.
Martine L
ML
Lamfers
Department of Neurosurgery, Erasmus MC, Rotterdam, The Netherlands.
Anne
A
Kleijn
Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Frederick F
FF
Lang
Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Wai-Kwan Alfred
WK
Yung
Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Luis M
LM
Vence
Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Candelaria
C
Gomez-Manzano
Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Juan
J
Fueyo
D056704:Adaptive Immunity / Q000276:immunology*; D000256:Adenoviridae / Q000276:immunology*; D000257:Adenoviridae Infections / Q000276:immunology; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005910:Glioma / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D050130:Oncolytic Virotherapy / Q000379:methods; D050504:Oncolytic Viruses / Q000276:immunology*
D000951:Antigens, Neoplasm