Compositions and methods for combination therapy with dengue virus and dendritic cells
Inventors
Assignees
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Publication Number
US-9730989-B2
Publication Date
2017-08-15
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 treating cancer in a subject by combining dendritic cell (DC) antigen presentation with administration of a Dengue Virus Type 2 serotype strain DENV-2 #1710. The method incubates DCs with at least one tumor cell antigen and then administers the Dengue Virus Type 2 serotype strain DENV-2 #1710 followed by administering the DCs. A second embodiment further includes lysing tumor tissue from the subject to form a lysis product comprising apoptotic or necrotic bodies, followed by incubating DCs with the lysis product.
DCs are prepared to present tumor-associated material, including tumor cell antigen and, in the lysis-product embodiment, apoptotic or necrotic bodies derived from tumor tissue. The DCs are administered after a subject temperature condition is met, including administering the DCs after the subject's temperature reaches 38 degrees Celsius or higher. The Dengue Virus Type 2 serotype strain DENV-2 #1710 is specifically defined as the Dengue Virus used in the method.
The provided content states that DV acts as an adjuvant to overcome tumor immune evasion and induces TH1/CTL- and LAK-activating apoptosis-associated pathways, including sTRAIL/TRAIL and cytokine cascades. The disclosure includes use in solid and blood cancers and describes embodiments covering DC pulsing with tumor cells, tumor lysates, and peptides, including MHC class I and II peptides.
Claims Coverage
Two independent claims are provided: clm-00001 and clm-00012. Together they define two core features centered on DCs incubated with tumor antigen material and administration of Dengue Virus Type 2 serotype strain DENV-2 #1710, with one claim also requiring DC administration after a subject temperature threshold is reached.
Dengue Virus Type 2 strain with tumor-antigen incubated dendritic cells
A method for treating cancer in a subject comprising incubating dendritic cells (DCs) with at least one tumor cell antigen, administering a Dengue Virus Type 2 serotype strain DENV-2 #1710 to a subject, and administering the DCs to the subject.
Apoptotic or necrotic body tumor lysis product with timed DC administration after fever threshold
A method for treating cancer in a subject comprising lysing tumor tissue from a subject to form a lysis product comprising apoptotic or necrotic bodies, incubating dendritic cells (DCs) with the lysis product, administering a Dengue Virus to the subject wherein the Dengue Virus is Dengue Virus Type 2 serotype strain DENV-2 #1710, and administering the DCs after the subject's temperature reaches 38 degrees Celsius or higher.
The claims collectively cover DENV-2 #1710 combined with DCs incubated with tumor cell antigen or tumor lysis product, including an embodiment with administration of the DCs after the subject's temperature reaches 38 degrees Celsius or higher.
Stated Advantages
DV acts as an adjuvant to overcome tumor immune evasion.
DV induces TH1/CTL- and LAK-activating apoptosis-associated pathways, including sTRAIL/TRAIL and cytokine cascades.
The disclosure reports reduced lung metastases in a mouse melanoma model comparing DV plus peptide-pulsed DC versus DC alone or control peptide.
Documented Applications
Use in solid and blood cancers.
Cancer types including leukemia, lymphoma, melanoma, breast cancer, prostate cancer, and brain cancer.
A mouse melanoma model comparing DV plus peptide-pulsed DC versus DC alone or control peptide.
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