Method for proliferation of antigen-specific T cells
Inventors
Karlsson-Parra, Alex • Wallgren, Anna-Carin • Andersson, Bengt
Assignees
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Publication Number
US-9211321-B2
Publication Date
2015-12-15
Expiration Date
Abstract
The present invention relates to an in vitro method for priming T cells suitable for administration to a patient having a tumor. The invention is also directed to the composition obtained by the method and uses thereof.
Core Innovation
The invention relates to an in vitro method for priming target T cells comprising antigen specific Th1 cells or cytotoxic T cells (CTLs) suitable for administration to a patient having a tumor. The method co-cultures target T cells from the patient with monocyte-derived dendritic cells from a first healthy donor and with autologous or allogeneic tumor material or tumor associated proteins or peptides.
In parallel, allogeneic lymphocytes are obtained by a mixed leukocyte reaction by culturing inactivated antigen presenting cells (APCs) from the donor with peripheral blood mononuclear cells (PBMCs) from a second healthy donor. The donor APCs express at least one MHC class II antigen identical with an MHC class II antigen expressed on APCs from the patient to be treated, and the allogeneic lymphocytes are sensitized against the APCs from the first healthy donor.
The sensitized allogeneic lymphocyte population is used in the co-culture context such that it promotes increased proliferation and/or survival of the antigen-specific Th1 cells or CTLs. The described approach supports tumor antigen-specific type 1 immunity, and optionally includes a restimulation approach using new monocyte-derived dendritic cells together with new sensitized allogeneic lymphocytes.
Claims Coverage
The document provides two independent claims. Across these claims, the coverage centers on co-culturing patient target T cells with antigen-loaded monocyte-derived dendritic cells plus sensitized allogeneic lymphocytes generated in a mixed leukocyte reaction with MHC class II identity, to drive increased proliferation and/or survival of antigen-specific Th1 cells or CTLs.
In vitro priming with donor monocyte-derived dendritic cells, tumor material, and MLR-generated sensitized allogeneic lymphocytes
An in vitro method for priming target T cells comprising antigen specific Th1 cells or cytotoxic T cells (CTLs) suitable for administration to a patient having a tumor, comprising co-culturing target T cells from the patient with monocyte-derived dendritic cells from a first healthy donor, autologous or allogeneic tumor material or tumor associated proteins or peptides, and allogeneic lymphocytes obtained by a mixed leukocyte reaction comprising culturing inactivated antigen presenting cells (APCs) from the first healthy donor with peripheral blood mononuclear cells (PBMCs) from a second healthy donor.
MHC class II identical donor APCs to sensitize allogeneic lymphocytes
The APCs express at least one MHC class II antigen that is identical with an MHC class II antigen expressed on APCs from the patient to be treated, and the allogeneic lymphocytes are sensitized against the APCs from the first healthy donor.
Sensitized allogeneic lymphocytes promote increased proliferation and/or survival of antigen-specific Th1 or CTLs
The sensitized allogeneic lymphocytes promote increased proliferation and/or survival of the antigen-specific Th1 cells or CTLs.
In vitro priming using autologous monocyte-derived dendritic cells and MLR-generated sensitized allogeneic lymphocytes
An in vitro method for priming target T cells comprising antigen specific Th1 cells or cytotoxic T cells (CTLs) suitable for administration to a patient having a tumor, comprising co-culturing target T cells from the patient with autologous monocyte-derived dendritic cells from a first healthy donor, and allogeneic lymphocytes obtained by a mixed leukocyte reaction comprising culturing inactivated antigen presenting cells (APCs) from the first healthy donor with peripheral blood mononuclear cells (PBMCs) from a second healthy donor.
MHC class II identical antigen matching and sensitization against donor APCs
The APCs express at least one MHC class II antigen that is identical with an MHC class II antigen expressed on APCs from the patient to be treated, and the allogeneic lymphocytes are sensitized against the APCs from the first healthy donor.
Increased proliferation and/or survival of antigen-specific Th1 or CTLs
The sensitized allogeneic lymphocytes promote increased proliferation and/or survival of the antigen-specific Th1 cells or CTLs.
Across the independent claims, the claims converge on in vitro priming of antigen-specific Th1 cells or CTLs for tumor patients using co-culture with donor monocyte-derived dendritic cells loaded with tumor material or tumor associated proteins/peptides and allogeneic lymphocytes generated by an MLR using inactivated donor APCs and PBMCs from another donor, where the MLR donor APCs share identical MHC class II with the patient and the resulting sensitized allogeneic lymphocytes promote increased proliferation and/or survival of the antigen-specific Th1 cells or CTLs.
Stated Advantages
Increased proliferation and/or survival of the antigen-specific Th1 cells or CTLs.
Promotes increased proliferation and/or survival through sensitized allogeneic lymphocytes generated with MHC class II identical donor APCs.
Documented Applications
An in vitro priming method for antigen-specific Th1 cells or CTLs suitable for administration to a patient having a tumor.
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