Compositions and methods for combination therapy with dengue virus and dendritic cells
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Publication Number
US-10159727-B2
Publication Date
2018-12-25
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 disclosed invention relates to cancer immunotherapy that combines Dengue Virus serotype 2 (DENV-2), including DENV-2 strain #1710 isolated from a Vero cell line, with tumor antigen-pulsed dendritic cells (DCs). The concept includes administering DENV-2 to induce a systemic immune-activating, TH1-biased response, and administering primed or mature DCs that are pulsed with tumor antigens, including tumor cells or lysate and peptides.
The disclosed tumor antigens include tumor cell lysate and peptides, with examples such as melanoma gp100 and TRP-1 peptides. The combined approach is described to involve immune pathways including TH1 cytokines such as IL-2 and IFN-gamma and apoptosis or immune signaling such as sTRAIL/TRAIL. The DCs are described as being autologous or allogeneic, and collected via processing such as leukapheresis.
Cancer treatment scope is described for both solid and blood cancers, with examples including melanoma, breast, prostate, brain cancers, and leukemia or lymphoma. The partial content further describes formulations for subcutaneous delivery of a DENV-2 strain #1710 composition, including an amount range of 10^3 pfu/ml to 10^8 pfu/ml, and describes administration approaches and experimental observations such as reduced lung metastases in melanoma mouse models when combining DENV-2 with peptide-pulsed DCs versus controls.
Claims Coverage
Two independent claims are identified. Across the independent claim families, the core inventive coverage centers on a subcutaneous-delivery cancer composition comprising Dengue Virus serotype 2 (DENV-2) strain #1710 isolated from a Vero cell line, with one family additionally requiring a specified DENV-2 amount range.
Subcutaneous DENV-2 strain composition isolated from Vero cell line
A composition formulated for subcutaneous delivery to a subject having a cancer, comprising Dengue Virus serotype 2 (DENV-2) strain #1710 isolated from a Vero cell line.
Subcutaneous DENV-2 strain composition with defined concentration range
A composition formulated for subcutaneous delivery to a subject having a cancer, comprising DENV-2 strain #1710 present in an amount of 10^3 pfu/ml to 10^8 pfu/ml, wherein the DENV-2 strain #1710 is isolated from a Vero cell line.
The independent claims primarily cover a subcutaneous-delivery cancer composition containing DENV-2 strain #1710 isolated from a Vero cell line, optionally limited by a concentration range (10^3 pfu/ml to 10^8 pfu/ml) in one independent claim family. Dependent claim refinements within the provided partial content specify cancer categories, including solid and blood cancers, leukemia or lymphoma, and specific solid cancer types, and further constrain attributes such as whether the DENV-2 strain is not attenuated and include dosing or volume details.
Stated Advantages
Reduced lung metastases in melanoma mouse models when comparing the combined approach versus controls.
Documented Applications
Cancer immunotherapy combining DENV-2 with tumor antigen-pulsed dendritic cells for treating subjects having cancer, including solid cancers and blood cancers.
Melanoma model use case where the combination is described to reduce lung metastases.
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