TY - JOUR
T1 - Localized treatment with oncolytic adenovirus delta-24-RGDOX induces systemic immunity against disseminated subcutaneous and intracranial melanomas
AU - Jiang, Hong
AU - Shin, Dong Ho
AU - Nguyen, Teresa T.
AU - Fueyo, Juan
AU - Fan, Xuejun
AU - Henry, Verlene
AU - Carrillo, Caroline C.
AU - Yi, Yanhua
AU - Alonso, Marta M.
AU - Collier, Tiara L.
AU - Yuan, Ying
AU - Lang, Frederick F.
AU - Gomez-Manzano, Candelaria
N1 - Funding Information:
We thank Joe Munch (the Department of Scientific Publications, MD Anderson Cancer Center) for editing the manuscript. This work was supported in part by NIH/NCI grants P50CA127001 and Cancer Center Support Grant
Funding Information:
We thank Joe Munch (the Department of Scientific Publications, MD Anderson Cancer Center) for editing the manuscript. This work was supported in part by NIH/NCI grants P50CA127001 and Cancer Center Support Grant P30CA016672 (Research Animal Support Facility, Small Animal Imaging Facility), the Cancer Prevention and Research Institute of Texas (RP170066), the Department of Defense (Team Science Award CA160525), the Marnie Rose Foundation, the J.P. Harris Brain Tumor Research Fund, the Bradley Zankel Foundation, the Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship (Parent F31: 1 F31 CA228207 01A1), the American Legion Auxiliary Fellowship in Cancer Research, and Terry and Janet Klebe Fellowship.
Funding Information:
P30CA016672 (Research Animal Support Facility, Small Animal Imaging Facility), the Cancer Prevention and Research Institute of Texas (RP170066), the Department of Defense (Team Science Award CA160525), the Marnie Rose Foundation, the J.P. Harris Brain Tumor Research Fund, the Bradley Zankel Foundation, the Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship (Parent F31: 1 F31 CA228207 01A1), the American Legion Auxiliary Fellowship in Cancer Research, and Terry and Janet Klebe Fellowship.
Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2019/11/15
Y1 - 2019/11/15
N2 - Purpose: Intratumoral injection of oncolytic adenovirus Delta-24-RGDOX induces efficacious antiglioma immunity in syngeneic glioma mouse models. We hypothesized that localized treatment with the virus is effective against disseminated melanomas. Experimental Design: We tested the therapeutic effect of injecting Delta-24-RGDOX into primary subcutaneous (s.c.) B16-Red-FLuc tumors in s.c./s.c. and s.c./intracranial (i.c.) melanoma models in C57BL/6 mice. Tumor growth and in vivo luciferase-expressing ovalbumin-specific (OT-I/Luc) T cells were monitored with bioluminescence imaging. Cells were profiled for surface markers with flow cytometry. Results: In both s.c./s.c. and s.c./i.c. models, 3 injections of Delta-24-RGDOX significantly inhibited the growth of both the virus-injected s.c. tumor and untreated distant s.c. and i.c. tumors, thereby prolonging survival. The surviving mice were protected from rechallenging with the same tumor cells. The virus treatment increased the presence of T cells and the frequency of effector T cells in the virus-injected tumor and mediated the same changes in T cells from peripheral blood, spleen, and brain hemispheres with untreated tumor. Moreover, Delta-24-RGDOX decreased the numbers of exhausted T cells and regulatory T cells in the virus-injected and untreated tumors. Consequently, the virus promoted the in situ expansion of tumor-specific T cells and their migration to tumors expressing the target antigen. Conclusions: Localized intratumoral injection of Delta-24-RGDOX induces an in situ antovaccination of the treated melanoma, the effect of which changes the immune landscape of the treated mice, resulting in systemic immunity against disseminated s.c. and i.c. tumors.
AB - Purpose: Intratumoral injection of oncolytic adenovirus Delta-24-RGDOX induces efficacious antiglioma immunity in syngeneic glioma mouse models. We hypothesized that localized treatment with the virus is effective against disseminated melanomas. Experimental Design: We tested the therapeutic effect of injecting Delta-24-RGDOX into primary subcutaneous (s.c.) B16-Red-FLuc tumors in s.c./s.c. and s.c./intracranial (i.c.) melanoma models in C57BL/6 mice. Tumor growth and in vivo luciferase-expressing ovalbumin-specific (OT-I/Luc) T cells were monitored with bioluminescence imaging. Cells were profiled for surface markers with flow cytometry. Results: In both s.c./s.c. and s.c./i.c. models, 3 injections of Delta-24-RGDOX significantly inhibited the growth of both the virus-injected s.c. tumor and untreated distant s.c. and i.c. tumors, thereby prolonging survival. The surviving mice were protected from rechallenging with the same tumor cells. The virus treatment increased the presence of T cells and the frequency of effector T cells in the virus-injected tumor and mediated the same changes in T cells from peripheral blood, spleen, and brain hemispheres with untreated tumor. Moreover, Delta-24-RGDOX decreased the numbers of exhausted T cells and regulatory T cells in the virus-injected and untreated tumors. Consequently, the virus promoted the in situ expansion of tumor-specific T cells and their migration to tumors expressing the target antigen. Conclusions: Localized intratumoral injection of Delta-24-RGDOX induces an in situ antovaccination of the treated melanoma, the effect of which changes the immune landscape of the treated mice, resulting in systemic immunity against disseminated s.c. and i.c. tumors.
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U2 - 10.1158/1078-0432.CCR-19-0405
DO - 10.1158/1078-0432.CCR-19-0405
M3 - Article
C2 - 31455679
AN - SCOPUS:85075093002
SN - 1078-0432
VL - 25
SP - 6801
EP - 6814
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 22
ER -