Use of MVA or MVADELTAE3L as immunotherapeutic agents against solid tumors
Inventors
Deng, Liang • Wolchok, Jedd • Merghoub, Taha • Shuman, Stewart • DAI, Peihong • Wang, Weiyi
Assignees
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Publication Number
US-12397029-B2
Publication Date
2025-08-26
Expiration Date
Abstract
The present disclosure relates to modified vaccinia Ankara (MVA) virus or MVAΔE3L delivered intratumorally or systemically as an anticancer immunotherapeutic agent, alone, or in combination with one or more immune checkpoint blocking agents for the treatment of malignant solid tumors. Particular embodiments relate to mobilizing the host's immune system to mount an immune response against the tumor.
Core Innovation
The invention relates to a method of eliciting an immune response in a subject with a solid malignant tumor by delivering to the tumor cells a therapeutically effective amount of modified vaccinia Ankara virus with deletion of vaccinia virulence factor E3 (MVAΔE3L). The approach targets solid malignant tumors and is framed as an immune-response elicitation method based on the use of MVAΔE3L.
Mechanistically, MVA/MVAΔE3L trigger type I interferon and inflammatory cytokine/chemokine responses via cGAS-STING. For MVAΔE3L, the response is also associated with dsRNA sensing via MDA5/MAVS, and the described downstream tumor effects include apoptosis of tumor cells.
The disclosed treatment further modulates the tumor microenvironment and generates systemic antitumor immunity. The document describes reduced regulatory CD4+ T cells and tumor-associated macrophages, increased effector CD8+ and CD4+ T cells, and dendritic cell maturation, together with effects on non-injected distant tumors and inhibition of metastasis.
Claims Coverage
The document includes two independent claims, covering 1) an MVAΔE3L-based immune response method for solid malignant tumors and 2) an MVAΔE3L plus immune checkpoint modulation combination method.
Eliciting an immune response with MVAΔE3L delivered to tumor cells
Delivering to tumor cells of a subject with a solid malignant tumor a therapeutically effective amount of modified vaccinia Ankara virus with deletion of vaccinia virulence factor E3 (MVAΔE3L).
Conjoint administration of MVAΔE3L with immune checkpoint modulation
Delivering to the tumor cells of the subject a therapeutically effective amount of modified vaccinia Ankara virus with deletion of vaccinia virulence factor E3 (MVAΔE3L), and conjointly administering to the subject a therapeutically effective amount of an immune checkpoint blocking agent or an immune checkpoint agonist.
Across the independent claims, the core coverage centers on delivering MVAΔE3L to tumor cells to elicit an immune response in solid malignant tumors, including a combination pathway where MVAΔE3L is conjointly administered with an immune checkpoint blocking agent or an immune checkpoint agonist.
Stated Advantages
Promotes apoptosis of tumor cells.
Modulates the tumor microenvironment, including reducing regulatory CD4+ T cells and tumor-associated macrophages and increasing effector CD8+ and CD4+ T cells and dendritic cell maturation.
Generates systemic antitumor immunity that affects non-injected distant tumors.
Inhibits metastasis.
Provides tumor regression/eradication and survival benefit in described in vivo settings.
Documented Applications
Treatment of solid malignant tumors using intratumoral or systemic delivery of MVAΔE3L, including combinations with immune checkpoint blockade.
Use in melanoma and colon carcinoma contexts, including effects on tumor regression/eradication, survival, immune infiltrate changes, control of non-injected distant tumors, and metastasis inhibition as described in vivo results.
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