Means and methods for active cellular immunotherapy of cancer by using tumor cells killed by high hydrostatic pressure and dendritic cells
AssigneeSOTIO a.s.
InventorsJirina BARTÛ{hacek over (N)}KOVÁ, Radek {hacek over (S)}PÍ{hacek over (S)}EK
Life of this patent
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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.
Claims21
1-28. (canceled)
A method of treating a human patient by cancer vaccination, wherein said method comprises the step of administering a pharmaceutical composition for inducing an immune response against tumor cells in a patient in need thereof comprising:
- a) tumor cells isolated from tumor cell lines or from a tumor tissue obtained from the patient to be treated and rendered apoptotic from in vitro treatment for 10 minutes to 2 hours with a high hydrostatic pressure (HHP) that ranges from 100 MPa to 300 MPa and
- b) human dendritic cells having said apoptotic tumor cells loaded thereon ex vivo,
- wherein said apoptotic tumor cells induce a higher level of phagocytosis by said dendritic cells as compared to tumor cells treated with UV irradiation,
- further wherein prior to loading, said apoptotic tumor cells are confirmed by clonogenic assay to be incapable of growing and forming a metastatic tumor after application to the patient, and further wherein the resulting dendritic cells have an at least 1.3 fold increase of activation markers CD86 and/or HLA-DR compared to dendritic cells loaded with tumor cells treated with UV irradiation,
- to the patient as a cancer vaccine.
A method of treating a human patient by cancer vaccination, wherein said method comprises the step of administering an ex vivo generated composition for inducing an immune response against tumor cells in a patient in need thereof, said composition comprising mature human dendritic cells produced by
- (a) pulsing ex vivo immature dendritic cells with tumor cells that, prior to pulsing, are first obtained from a tumor cell line or from a tumor tissue isolated from the patient being treated and then rendered apoptotic from in vitro treatment for 10 to 2 hours with a high hydrostatic pressure (HHP) that ranges from 100 MPa to 300 MPa, and wherein the resulting HHP treated tumor cells are enriched for expression of HSP70, HSP90 or calreticulin compared to expression in tumor cells treated by UV irradiation or anthracyclines and
- (b) allowing said ex vivo dendritic cells to mature, wherein said mature dendritic cells are able to induce CD4 and CD8-mediated tumor specific T-cell responses without inducing potentially harmful regulatory T-cells at levels that could inhibit the anti-tumor immune response,
- to the patient as a cancer vaccine.
Dependencies are inferred from the claim text.