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Updated: Sep 16, 2025
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Oncolytic adenovirus serotype 35 mediated tumor growth suppression via efficient activation of antitumor immunity
Ryosuke Ono1, Sora Tokuoka2, Masashi Tachibana1,2
1Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, The University of Osaka, Osaka, Japan.
Background:
Oncolytic adenoviruses (OAds) mediate superior antitumor effects both by inducing direct oncolysis and activating antitumor immunity. Previously, we developed a novel OAd fully composed of human adenovirus serotype 35 (OAd35). OAd35 efficiently killed a variety of human tumor cells; however, OAd35-mediated activation of antitumor immunity remains to be evaluated. In this study, we examined whether OAd35-induced activation of immune cells contributes to the antitumor effects of OAd35.
Methods:
Tumor infiltration and activation of immune cells following intratumoral administration of OAd35 in tumor-bearing immune-competent and nude mice were analyzed. The involvement of immune cells in the tumor growth-suppression effects of OAd35 was evaluated in asialo GM1 (aGM1)+ cell-depleted mice. The key signals for the OAd35-mediated tumor infiltration of NK cells were examined in interferon (IFN) alpha and beta receptor subunit 1 (IFNAR1) knockout and toll-like receptor 9 knockout mice.
Results:
OAd35 efficiently induced tumor infiltration of activated natural killer (NK) cells and T cells after intratumoral administration in B16 tumor-bearing mice. Depletion of aGM1+ cells, including NK cells and a portion of CD8+ T cells, significantly hindered the OAd35-mediated tumor growth suppression in C57BL/6J wild-type mice and BALB/c nude mice. In IFNAR1 knockout mice, OAd35-induced tumor infiltration of activated NK cells and OAd35-mediated tumor growth suppression were significantly attenuated.
Conclusions:
These data described above suggested that immune cells, including aGM1+ cells, contributed to the antitumor effects of OAd35. OAd35 significantly promoted activation and tumor infiltration of NK cells. The type-I IFN signal was crucial for the OAd35-mediated tumor infiltration, activation of NK cells, and tumor growth suppression. These findings suggest that OAd35 is a promising cancer immunotherapy agent via its enhancement of the antitumor activities of immune cells.
Insights
Oncolytic adenovirus OAd35 activates immune cells, including natural killer (NK) cells, to suppress tumor growth. Type-I interferon signaling is essential for OAd35
Area of Science:
- Oncolytic virotherapy
- Immunooncology
Background:
- Oncolytic adenoviruses (OAds) offer dual antitumor mechanisms: direct tumor cell lysis and immune system activation.
- Human adenovirus serotype 35 (OAd35) is a novel OAd with demonstrated tumor cell killing capabilities.
- The role of OAd35 in activating antitumor immunity requires further investigation.
Purpose of the Study:
- To investigate whether OAd35-induced immune cell activation contributes to its antitumor effects.
- To evaluate the specific immune cell populations involved in OAd35's therapeutic action.
Main Methods:
- Intratumoral administration of OAd35 in tumor-bearing immune-competent and nude mice.
- Analysis of immune cell infiltration and activation post-treatment.
- Assessment of OAd35's efficacy in immune cell-depleted (asialo GM1+) and knockout (IFNAR1, TLR9) mouse models.
Main Results:
- OAd35 treatment led to significant infiltration and activation of natural killer (NK) cells and T cells in tumors.
- Depletion of asialo GM1+ cells (including NK cells) impaired OAd35-mediated tumor growth suppression.
- Absence of Type-I interferon signaling (IFNAR1 knockout) markedly reduced NK cell infiltration, activation, and OAd35's antitumor effects.
Conclusions:
- Immune cells, particularly NK cells, play a crucial role in the antitumor efficacy of OAd35.
- Type-I interferon signaling is indispensable for OAd35-induced NK cell responses and tumor growth inhibition.
- OAd35 demonstrates significant potential as a cancer immunotherapy agent by enhancing antitumor immune activity.
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