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Updated: Jul 13, 2025
Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Dual-Armed Oncolytic Myxoma Virus Encoding IFN-γ and CD47 Promotes Lymphocyte Infiltration and Tumor Suppression of
Jong Kyu Woo1, Tae-Geuk Kim1, Na Yeon Im1
1ViroCure, #502, Ace TwinTower 1, 285 Digital-ro, Guro-gu, Seoul 08381, Republic of Korea.
Abstract:
Myxoma virus (MyxV) is a rabbit-specific poxvirus. However, its ability to selectively target tumor cells has established it as a safe and effective anticancer therapy. To strengthen its preclinical efficacy, transgenes that can prolong cancer cell infection and enhance anti-tumor effector functions are currently being investigated. We engineered MyxV armed with CD47, to turn on a 'do not eat me' signal within infected cells with actively replicating viruses, and with IFN-γ to further activate host immune anticancer responses. Tumor suppressive activities were significantly enhanced by the dual-armed MyxV_CD47/IFN-γ compared to parental MyxV or single-armed MyxV_CD47 or MyxV_IFN-γ. In addition, significant increases in IFN-γ+ CD8+T-cells and CD4+ T-cells populations within tumor-infiltrating lymphocytes (TIL) were observed after MyxV_CD47/IFN-γ treatment. Notably, all groups treated with MyxV showed a marked reduction in Foxp3+ CD4+ regulatory T-cells (Tregs) within TIL. We also show that MyxV infection induces PD-L1 up-regulation in cancer cells, and combinational treatment of MyxV with anti-mouse PD-L1 antibodies (αPD-L1) further controlled tumor burden and increased survival in the syngeneic melanoma model B16F10. Our data demonstrate that a CD47 and IFNγ dual-armed MyxV is an effective oncolytic viral immunotherapeutic. These findings strongly support further preclinical investigations to develop next-generation MyxV-based immunotherapy approaches.
Insights
Engineered Myxoma virus (MyxV) armed with CD47 and IFN-γ enhances anticancer therapy by prolonging tumor cell infection and boosting immune responses. This dual-armed MyxV shows significant tumor suppression and improved survival in preclinical models.
Area of Science:
- Oncolytic virotherapy
- Cancer immunotherapy
- Viral vector engineering
Background:
- Myxoma virus (MyxV) is a rabbit-specific poxvirus with selective tumor-targeting capabilities.
- Enhancing MyxV's preclinical efficacy involves engineering transgenes to prolong infection and boost anti-tumor immunity.
Purpose of the Study:
- To engineer MyxV armed with CD47 and Interferon-gamma (IFN-γ) to enhance its anticancer properties.
- To evaluate the efficacy of dual-armed MyxV_CD47/IFN-γ in preclinical cancer models.
Main Methods:
- Engineered MyxV with CD47 ('do not eat me' signal) and IFN-γ (immune activation).
- Assessed tumor suppressive activities of parental MyxV, MyxV_CD47, MyxV_IFN-γ, and MyxV_CD47/IFN-γ.
- Analyzed tumor-infiltrating lymphocytes (TILs), including CD8+ T-cells, CD4+ T-cells, and regulatory T-cells (Tregs).
- Investigated PD-L1 expression and combined MyxV treatment with anti-PD-L1 antibodies.
Main Results:
- Dual-armed MyxV_CD47/IFN-γ demonstrated significantly enhanced tumor suppressive activities compared to single-armed or parental MyxV.
- Treatment increased populations of IFN-γ+ CD8+ T-cells and CD4+ T-cells within TILs.
- All MyxV treatments reduced Tregs within TILs.
- MyxV infection upregulated PD-L1 on cancer cells; combination with anti-PD-L1 improved tumor control and survival.
Conclusions:
- A CD47 and IFN-γ dual-armed MyxV is an effective oncolytic viral immunotherapeutic.
- This engineered MyxV enhances anti-tumor immune responses and reduces regulatory T-cells.
- Findings support further preclinical development of next-generation MyxV-based immunotherapies.
