Combination immunotherapies for treatment of cancer
Inventors
Assignees
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Publication Number
US-11357795-B2
Publication Date
2022-06-14
Expiration Date
Abstract
Described herein are compositions and methods for treating a disease, particularly a cancer, with an immune checkpoint modulatory agent and a strain of an Arbovirus or a strain of an Alphavirus. Also provided herein are also methods for combination therapy comprising administration of an immune checkpoint modulatory agent, tumor antigen primed dendritic cells and an Alphavirus or an Arbovirus.
Core Innovation
The disclosed subject matter relates to a method for treatment of cancer by administering a Dengue virus to a subject who has received an immune checkpoint modulatory agent, where the immune checkpoint modulatory agent is an antibody against PD1. The disclosure also relates to Dengue virus pharmaceutical compositions, including liquid and lyophilized preparations with lyoprotectants and excipient classes, and the lyophilized compositions are reconstituted to an isotonic target upon reconstitution.
The disclosure further provides delivery formats and related components for administering Dengue virus, including parenteral administration routes and inhalation dry powder formulations. Storage containers and kit components are described, including a sterile container and a kit including a Dengue virus composition together with an immune checkpoint inhibitor, with optional inclusion of immune cells.
The document discusses Dengue virus activation and immune pathway effects in the context of tumor antigen-primed dendritic cells, with DC-mediated immune responses being enhanced. It further discusses immune effects associated with Dengue virus, including TH1-associated responses and changes associated with antigen presentation markers, and relates these effects to overcoming tumor immune evasion and enhancing DC/CTL responses.
Claims Coverage
The claim set includes one independent claim directed to a cancer treatment method using Dengue virus after immune checkpoint modulatory therapy, where the immune checkpoint modulatory agent is an antibody against PD1. Four dependent inventive features further refine the claim by specifying Dengue virus amount, administration volume, a designated Dengue virus, and selected cancer histologies and metastatic disease.
Prior PD1 antibody immune checkpoint modulation followed by Dengue virus
A method for treatment of cancer comprising administering a Dengue virus to a subject having received an immune checkpoint modulatory agent, wherein the immune checkpoint modulatory agent is an antibody against PD1.
Dengue virus titer range in PFU/mL
The method of treatment uses a Dengue virus amount of about 10^2 to about 10^8 plaque-forming units (PFU)/mL.
Dengue virus administration volume range
The method uses Dengue virus present in a volume of about 0.01 mL to about 0.1 mL.
Specific Dengue virus designation
The method specifies use of a Dengue virus designated as 45AZ5.
Selected cancer histology range
The method is applied to a cancer selected from small cell lung cancer, non-small cell lung cancer (NSCLC), mesothelioma, squamous cell carcinoma, adenocarcinoma, or large cell carcinoma.
Metastatic cancer treatment
The method is applied to cancer that is metastatic.
Overall, the claims cover administering Dengue virus to cancer patients who have already received PD1 antibody immune checkpoint modulation, with dependent refinements specifying Dengue virus PFU/mL range, administration volume range, a particular Dengue virus designation, and narrowing the target indication to selected cancer histologies and metastatic disease.
Stated Advantages
Overcomes tumor immune evasion and enhances DC/CTL responses.
Improves immune responses associated with tumor antigen-primed dendritic cells and checkpoint-modulatory contexts.
Reduces lung metastases in mouse melanoma models.
Enhances DC-mediated anti-cancer activity and DC-related cytokine induction, including IL-12p70.
Documented Applications
Cancer immunotherapy method for treating cancer in a subject receiving an immune checkpoint modulatory agent (PD1 antibody), including metastatic disease.
Treatment of small cell lung cancer, non-small cell lung cancer (NSCLC), mesothelioma, squamous cell carcinoma, adenocarcinoma, or large cell carcinoma in the disclosed method.
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