Means and methods for active cellular immunotherapy of cancer by using tumor cells killed by high hydrostatic pressure and dendritic cells
Inventors
BARTUNKOVÁ JIRINA, null • Bartů{hacek over (n)}ková, Ji{hacek over (r)}ina • ŠPÍŠEK RADEK, null • {hacek over (S)}PÍ{hacek over (S)}EK, Radek
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10905751-B2
Publication Date
2021-02-02
Expiration Date
Abstract
Disclosed are pharmaceutical compositions for inducing an immune response against tumor cells comprising tumor cells which are made apoptotic by treatment with high hydrostatic pressure and dendritic cells, and methods for producing such compositions.
Core Innovation
The invention relates to a method for treating cancer in a patient in need thereof by preparing immature dendritic cells from monocytes obtained from the patient. The monocytes are cultured in the presence of GM-CSF and IL-4 to obtain an immature dendritic cell.
Tumor cells are obtained from the patient or from one or more tumor cell lines, and apoptosis is induced in the tumor cells by applying high hydrostatic pressure. The apoptotic tumor cells are then used to load the immature dendritic cells in vitro to obtain a loaded dendritic cell, wherein the immature dendritic cell is combined with the apoptotic tumor cell at a ratio between about 1:1 to about 10:1.
The loaded dendritic cells are further matured in vitro by treating the loaded dendritic cells with Poly I:C or LPS to obtain a loaded mature dendritic cell. Finally, a therapeutically effective amount of the mature loaded dendritic cell is administered to the patient to induce anti-tumor immunity.
Claims Coverage
The document provides one independent claim covering a multi-step immunotherapy workflow with defined steps for monocyte-to-immature dendritic cell generation, induction of tumor-cell apoptosis by high hydrostatic pressure, in vitro dendritic cell loading, in vitro maturation using Poly I:C or LPS, and administration of a therapeutically effective amount to a patient. The dependent claims refine this framework by adding constraints on pressure/time, dendritic-cell:tumor-cell loading ratio, immunological outcome characteristics, and specified administration routes.
Patient-derived monocytes cultured with GM-CSF and IL-4 to obtain immature dendritic cells
A method in which a monocyte from the patient is cultured in the presence of GM-CSF and IL-4 to obtain an immature dendritic cell.
High hydrostatic pressure-induced apoptosis of tumor cells
Apoptosis is induced in a tumor cell by applying high hydrostatic pressure.
In vitro loading of immature dendritic cells with apoptotic tumor cells at a defined ratio
An immature dendritic cell is loaded in vitro with the apoptotic tumor cell to obtain a loaded dendritic cell, wherein the immature dendritic cell is combined with the apoptotic tumor cell at a ratio between about 1:1 to about 10:1.
In vitro maturation using Poly I:C or LPS to obtain loaded mature dendritic cells
The loaded dendritic cell is further matured in vitro by treating the loaded dendritic cell with Poly I:C or LPS in vitro to obtain a loaded mature dendritic cell.
Administration of a therapeutically effective amount to treat cancer
A therapeutically effective amount of the mature loaded dendritic cell obtained in the method is administered to the patient.
Overall claim coverage centers on producing immature dendritic cells from patient monocytes (GM-CSF and IL-4), generating apoptotic tumor cells via high hydrostatic pressure, loading the immature dendritic cells with those apoptotic tumor cells at a defined ratio, maturing the loaded dendritic cells in vitro with Poly I:C or LPS, and administering the resulting mature loaded dendritic cells at a therapeutically effective amount to treat cancer.
Stated Advantages
Enhanced anti-tumor immunity indicated by increased tumor-specific T-cell responses, including IFN-γ producing tumor-specific CD4/CD8 T cells.
Reduced regulatory T-cell expansion characterized by reduced FoxP3+ Tregs compared with a comparator dendritic cell loading approach using UV-irradiated tumor cells.
Increased immunogenic cell-death marker expression and release, including hsp70/hsp90/calreticulin and HMGB1 release.
Enhanced phagocytosis and dendritic cell maturation associated with the apoptotic tumor cell loading approach.
Clinical outcomes indicating prolonged PSA doubling time and median survival versus expectations/controls in patient data.
Documented Applications
Use as a cancer immunotherapy method involving administration of mature loaded dendritic cells prepared from monocytes and tumor cells to induce anti-tumor immunity.
Application to ovarian cancer and prostate cancer contexts as described in the provided content.
Application to acute lymphoblastic leukemia as described in the provided content.
Interested in licensing this patent?