Compositions and methods for combination therapy with dengue virus and dendritic cells
Inventors
Assignees
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Publication Number
US-9849167-B2
Publication Date
2017-12-26
Expiration Date
Abstract
Described herein are compositions and methods for treating cancer through the combination of tumor antigen-pulsed dendritic cells and Dengue Virus. The combination of the two forms of therapeutic intervention provides enhanced tumor cell reduction compared to either alone. The cancer targeted by compositions and methods described herein may be a solid cancer or blood cancer.
Core Innovation
The invention relates to a method for reducing or treating cancer in a subject in need thereof by using a Dengue Virus as an adjuvant for an immunotherapy for cancer treatment. The method includes subcutaneously administering an effective amount of the Dengue Virus to the subject, and the Dengue Virus is provided in an amount in the range of 10^3 pfu/ml to 10^8 pfu/ml.
The disclosed immunotherapy includes tumor antigen-pulsed dendritic cells delivered to the subject. The dendritic cells are pulsed with tumor-derived antigens including peptides and tumor cell material such as lysates, apoptotic bodies, or necrotic bodies derived from tumor tissue, and the antigen presentation includes MHC class I and MHC class II.
The disclosed combination is described for targeting both solid cancer and blood cancer. Solid cancer examples include melanoma, breast cancer, prostate cancer, and brain cancer, and blood cancer examples include leukemia and lymphoma. Experimental support is provided in a mouse melanoma model, where combining DENV-2 strain #1710 with antigen-pulsed dendritic cells is described as reducing lung metastases compared with dendritic cells alone or control-peptide/dendritic cell conditions.
Claims Coverage
The independent claim identifies a cancer treatment method using a Dengue Virus as an adjuvant combined with an immunotherapy, with a specified Dengue Virus concentration range. The inventive features are further refined in dependent claims by tightening the Dengue Virus dose range, specifying Dengue Virus serotypes and a specific DENV-2 strain, and narrowing the cancer targets and viral attenuation status.
Subcutaneous Dengue Virus adjuvant for cancer immunotherapy
A method for reducing or treating cancer in a subject comprising subcutaneously administering an effective amount of a Dengue Virus as an adjuvant to an immunotherapy for treatment of cancer.
Dengue Virus amount range 10^3 pfu/ml to 10^8 pfu/ml
The method of subcutaneous Dengue Virus adjuvant administration where the Dengue Virus is present in an amount of 10^3 pfu/ml to 10^8 pfu/ml.
Dengue Virus concentration between 10^3 pfu/ml and 10^6 pfu/ml
The method where the Dengue Virus is present at a concentration between 10^3 pfu/ml and 10^6 pfu/ml.
Permitted Dengue Virus serotypes
The method where the Dengue Virus is of serotypes DENV-1, DENV-2, DENV-3, or DENV-4.
DENV-2 strain #1710
The method where the Dengue Virus is the DENV-2 strain #1710.
Solid cancer targeting to specific cancer types
The method where the solid cancer is lung cancer, breast cancer, melanoma, or prostate cancer.
Non-attenuated Dengue Virus
The method where the Dengue Virus is not attenuated.
Overall, the claim set centers on subcutaneous administration of a Dengue Virus as an adjuvant to cancer immunotherapy, with a defined Dengue Virus amount range and dependent refinements specifying narrower concentrations, allowed Dengue Virus serotypes, the particular DENV-2 strain #1710, specific solid cancer types, and a constraint that the Dengue Virus is not attenuated.
Stated Advantages
Reduced lung metastases when combining DENV-2 strain #1710 with antigen-pulsed dendritic cells versus dendritic cells alone or control-peptide/dendritic cell conditions.
Documented Applications
Cancer treatment by reducing or treating cancer in a subject using Dengue Virus as an adjuvant to immunotherapy with tumor antigen-pulsed dendritic cells for both solid cancer and blood cancer targets.
Targeting solid cancers including melanoma, breast cancer, prostate cancer, and brain cancer.
Targeting blood cancers including leukemia and lymphoma.
Mouse melanoma model evaluation showing reduced lung metastases in the combination condition.
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