Research output: Contribution to journal › Article › peer-review
Ad6-Based GM-CSF Expressing Vector Displays Oncolytic and Immunostimulatory Effects in an Immunocompetent Syrian Hamster Model of Cholangiocarcinoma. / Zabelina, Daria S.; Osipov, Ivan D.; Maslov, Denis E. et al.
In: Viruses, Vol. 17, No. 2, 162, 24.01.2025.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Ad6-Based GM-CSF Expressing Vector Displays Oncolytic and Immunostimulatory Effects in an Immunocompetent Syrian Hamster Model of Cholangiocarcinoma
AU - Zabelina, Daria S.
AU - Osipov, Ivan D.
AU - Maslov, Denis E.
AU - Kovner, Anna V.
AU - Vasikhovskaia, Valeriia A.
AU - Demina, Diana S.
AU - Romanov, Stanislav E.
AU - Shishkina, Ekaterina V.
AU - Davydova, Julia
AU - Netesov, Sergey V.
AU - Romanenko, Margarita V.
N1 - This research has been supported by the Russian Ministry of Science and Higher Education grants FSUS-2020-0035, FSUS-2022-0021, and FSUS-2025-0012. Additional support was provided by the University of Minnesota Masonic Cancer Center and National Institute of Health R01CA276179.
PY - 2025/1/24
Y1 - 2025/1/24
N2 - Cholangiocarcinoma (CCA), the second most common liver cancer, remains highly resistant to chemotherapy and radiotherapy, leaving patients with unresectable tumors in urgent need of innovative therapeutic approaches. Adenovirus type 6 (Ad6), a species C human adenovirus, offers significant potential for cancer therapy due to its low seroprevalence compared to Adenovirus type 5 (Ad5) and its ability to evade Kupffer cells during systemic delivery. In this study, we developed a novel oncolytic adenovirus vector based on the Ad6 engineered to express human GM-CSF (Ad6-d24-GM) and evaluated its therapeutic efficacy in a novel immunocompetent, replication-permissive Syrian hamster model of CCA. Intratumoral administration of Ad6-d24-GM significantly suppressed tumor growth and prolonged survival without evidence of toxicity, as indicated by stable body weights and normal liver enzyme levels. Both Ad6-d24-GM and wild-type Ad6 induced robust infiltration of CD4+ and CD8+ T cells, as well as CD68+ macrophages within tumors, demonstrating activation of antitumor immunity. Notably, the Ad6-d24-GM group exhibited a statistically significant increase in CD68+ cells compared to wild-type Ad6, highlighting the immunomodulatory effect of GM-CSF transgene. These results demonstrate the oncolytic and immunostimulatory potential of Ad6-based vectors for CCA treatment and validate the Syrian hamster syngeneic CCA-OF model as a valuable platform for studying oncolytic adenovirus therapies.
AB - Cholangiocarcinoma (CCA), the second most common liver cancer, remains highly resistant to chemotherapy and radiotherapy, leaving patients with unresectable tumors in urgent need of innovative therapeutic approaches. Adenovirus type 6 (Ad6), a species C human adenovirus, offers significant potential for cancer therapy due to its low seroprevalence compared to Adenovirus type 5 (Ad5) and its ability to evade Kupffer cells during systemic delivery. In this study, we developed a novel oncolytic adenovirus vector based on the Ad6 engineered to express human GM-CSF (Ad6-d24-GM) and evaluated its therapeutic efficacy in a novel immunocompetent, replication-permissive Syrian hamster model of CCA. Intratumoral administration of Ad6-d24-GM significantly suppressed tumor growth and prolonged survival without evidence of toxicity, as indicated by stable body weights and normal liver enzyme levels. Both Ad6-d24-GM and wild-type Ad6 induced robust infiltration of CD4+ and CD8+ T cells, as well as CD68+ macrophages within tumors, demonstrating activation of antitumor immunity. Notably, the Ad6-d24-GM group exhibited a statistically significant increase in CD68+ cells compared to wild-type Ad6, highlighting the immunomodulatory effect of GM-CSF transgene. These results demonstrate the oncolytic and immunostimulatory potential of Ad6-based vectors for CCA treatment and validate the Syrian hamster syngeneic CCA-OF model as a valuable platform for studying oncolytic adenovirus therapies.
KW - Syrian hamster
KW - adenovirus type 6 (HAdV-C6, Ad6)
KW - cancer
KW - cholangiocarcinoma
KW - immunotherapy
KW - liver cancer
KW - oncolytic virus
UR - https://www.mendeley.com/catalogue/183f7f2c-f74f-3276-915c-94b69433ebca/
UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85219048184&origin=inward&txGid=2e747d762e14072bb28141262f2efa50
U2 - 10.3390/v17020162
DO - 10.3390/v17020162
M3 - Article
VL - 17
JO - Viruses
JF - Viruses
SN - 1999-4915
IS - 2
M1 - 162
ER -
ID: 64946116