Method of producing immunotherapy vaccine
Inventors
Sakuma, Sadatoshi • OSONO, Michiyo • OKA, Eriko
Assignees
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Publication Number
US-11642402-B2
Publication Date
2023-05-09
Expiration Date
Abstract
A method of producing an immunotherapy vaccine is provided. The method includes performing a heat treatment to exosomes separated from cancer cells or body fluids including blood of a cancer patient to promote inactivation of proteolytic enzymes in the exosomes, and introducing or co-culturing the exosomes in dendritic cells derived from blood of the cancer patient or a healthy person to make antigen-presenting cells.
Core Innovation
The invention relates to a method of producing an immunotherapy vaccine using exosomes separated from cancer cells or bodily fluids from a cancer patient. The method performs a heat treatment under a condition of 56° C for 30 minutes on the exosomes to promote inactivation of proteolytic enzymes in the exosomes.
The resulting exosomes are used in combination with dendritic cells to enable antigen presentation. The method further includes introducing or co-culturing the heat-treated exosomes in the presence of dendritic cells derived from blood from the cancer patient or a healthy person to make antigen-presenting cells.
The described motivation includes low DC/cancer fusion efficiency, issues with cancer-derived exosomes escaping antigen presentation, and storage/instability problems. Supporting observations described include membrane preservation limitations after heating, increased exosomal protein expression after heating, and CTL lysis assay results indicating enhanced tumor lysis.
Claims Coverage
One independent claim is identified. It is centered on 2 inventive features: heat treatment of exosomes under a defined condition to promote inactivation of proteolytic enzymes, and use of the treated exosomes with dendritic cells to make antigen-presenting cells.
Heat treatment to inactivate proteolytic enzymes in exosomes
Performing a heat treatment under a condition of 56° C for 30 minutes on exosomes separated from cancer cells or bodily fluids from a cancer patient to promote inactivation of proteolytic enzymes in the exosomes.
Introducing or co-culturing treated exosomes with dendritic cells to make antigen-presenting cells
Introducing or co-culturing the exosomes in the presence of dendritic cells derived from blood from the cancer patient or a healthy person to make antigen-presenting cells.
The claim coverage concentrates on a defined heat treatment condition for cancer-related exosomes and use of those treated exosomes with dendritic cells derived from the cancer patient or a healthy person to produce antigen-presenting cells.
Stated Advantages
Enhanced tumor lysis in CTL lysis assay results is described, including tumor lysis comparable or superior to PEG fusion/co-culture.
Increased exosomal protein expression after heating is described.
Exosome membrane integrity is described as being maintained up to a limit, based on microphotographs showing membrane preservation limitations.
Promotion of antigen presentation from cancer-derived exosomes is described as addressing exosomes escaping antigen presentation.
Documented Applications
Use in producing an immunotherapy vaccine based on heat-treated exosomes and dendritic-cell-derived antigen-presenting cells.
Generation of cytotoxic T cells via co-culture steps is discussed as an optional downstream use case within the described workflow.
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