Method for treating cancer using dengue virus serotype 1 (DENV-1)
Inventors
Assignees
Prime Vax Immuno Oncology Inc • PrimeVax Immuno Oncology Inc
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Publication Number
US-12059443-B2
Publication Date
2024-08-13
Expiration Date
Abstract
Described herein are compositions and methods for treating a disease, particularly a cancer, with a Dengue Virus and, optionally, primed dendritic cells recognizing a tumor antigen. Lysis protocols are described where the lysis does not result in complete or less than complete lysis of cells in order to provide cell surface molecules maintained in a cell surface-embedded state. Non-lethal Dengue virus strains are also provided for therapeutic purposes.
Core Innovation
The disclosed approach provides a method of treating a solid cancer by administering an effective amount of a Dengue virus serotype 1 strain. In particular, the solid cancer is a melanoma and the Dengue virus serotype 1 strain is 45AZ5, with administration asserted to reduce a level of cancer cells and with the virus present in an amount up to about 90,000 PFU.
The disclosure further characterizes Dengue virus-based cancer immunotherapy using dengue virus serotypes and strains, including non-lethal dengue strains, with administered amounts described in terms of PFU and effective-dose ranges. It includes formulations and pharmaceutically acceptable excipients, and it describes administration formats including liquid and lyophilized or freeze-dried forms, as well as storage in containers such as syringes and vials.
The disclosure additionally describes a combination approach in which Dengue virus is used with tumor antigen-primed dendritic cell vaccination. It asserts immune activation and cytokine responses including TH1 cytokines and elevated IL-12p70, and associates these immune changes with increased Class I MHC, ICAM-1, and PD-L1 and reduced melanoma lung metastases in mice when combining Dengue virus with antigen-primed DCs.
The disclosed DC priming and combination context uses tumor antigens and maturation/danger signaling to induce elevated IL-12p70, and it includes immune outcome assertions such as enhanced CTL and NK-mediated melanoma cell killing with Dengue virus supernatants and DC/DV combination. It also includes IL-12p70 as a predictor of response and describes IL-12p70 thresholds, with multiple melanoma contexts discussed including V600E-positive melanoma and solid or metastatic cancer settings.
Claims Coverage
The partial claim set contains one independent claim, which provides the central therapeutic method. The independent claim is primarily centered on treating melanoma with a Dengue virus serotype 1 strain 45AZ5 at a specified PFU ceiling, with additional dependent claims refining measurable tumor or cancer-cell reduction and patient or treatment parameters.
Treating melanoma with dengue virus serotype 1 strain 45az5
A method of treating a solid cancer by administering to a solid cancer an effective amount of a Dengue virus serotype 1 strain, wherein the solid cancer is a melanoma, wherein the Dengue virus serotype 1 strain is 45AZ5, wherein the administering reduces a level of cancer cells, and wherein the Dengue virus serotype 1 strain is present in an amount up to about 90,000 PFU.
Ct-measured tumor size reduction threshold
The method further includes reducing a solid cancer’s size by at least about 60%, as measured by computed tomography (CT) scanning.
Higher ct-measured response threshold
The method further includes reducing a solid cancer’s size by at least about 90%, as measured by computed tomography (CT) scan.
V600e-positive melanoma selection
The method further includes that the melanoma is V600E positive.
Specified viral preparation volume range
The method further specifies that the Dengue virus serotype 1 strain is present in a volume of about 0.01 ml to 0.1 ml.
Subcutaneous injection administration route
The method is carried out by administering the Dengue virus serotype 1 strain to a subject via a subcutaneous injection.
Overall, the independent claim covers administering an effective amount of Dengue virus serotype 1 strain 45AZ5 to treat melanoma and reduce a level of cancer cells, with the virus present up to about 90,000 PFU. Dependent claims refine measurable outcomes using CT size reduction thresholds of about 60% and about 90%, restrict melanoma to V600E-positive, and further specify viral volume and subcutaneous injection administration.
Stated Advantages
Reduces a level of cancer cells.
Reduces a solid cancer’s size by at least about 60%, as measured by computed tomography (CT) scanning.
Reduces a solid cancer’s size by at least about 90%, as measured by computed tomography (CT) scan.
Predicts or correlates response with IL-12p70 thresholds, including IL-12p70 as a predictor of response.
Documented Applications
Treating a solid cancer, wherein the solid cancer is a melanoma.
Treating V600E-positive melanoma.
Dengue virus-based cancer immunotherapy described in combination with tumor antigen-primed dendritic cell vaccination for melanoma settings, including reduction of melanoma lung metastases in mice.
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