Method for priming of T cells
Inventors
Karlsson-Parra, Alex • Wallgren, Anna-Carin • Andersson, Bengt
Assignees
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Publication Number
US-10000736-B2
Publication Date
2018-06-19
Expiration Date
Abstract
The present invention relates to an in vitro method for priming T cells suitable for administration to a patient having a viral infection. The invention is also directed to the composition obtained by the method and uses thereof.
Core Innovation
The invention relates to antigen specific CD4+ and/or CD8+ T cells obtained by an in vitro method for priming of antigen specific CD4+ and/or CD8+ T cells for administration to a patient having a viral infection. The method uses co-culturing of target T cells from the patient, mature monocyte-derived dendritic cells from a first healthy donor, and virus material or virus associated proteins or peptides.
The co-culture further includes lymphocytes from a second healthy donor sensitized against MHC class I and/or MHC class II antigens on antigen presenting cells (APCs) from the first healthy donor, wherein the APCs are allogeneic with respect to the lymphocytes. The lymphocytes are obtained by culturing non-proliferating peripheral blood mononuclear cells (PBMCs) from the first healthy donor with PBMCs from the second healthy donor.
The described approach is an in vitro co-culture priming strategy to support antigen-specific T-cell generation for adoptive administration in the context of viral infection. Supporting description states that allosensitized allogeneic lymphocytes (ASALs) upregulate CD70 on DCs and increase IL-12, IFN-b3, and IL-2, correlating with enhanced CD27+ CD8+ T-cell generation, reduced apoptosis (Annexin-V), increased proliferation, and increased virus-specific CD8 frequencies after expansion and restimulation.
Claims Coverage
The independent claim defines an in vitro co-culture priming method that generates antigen specific CD4+ and/or CD8+ T cells for administration to a patient with a viral infection, incorporating four main inventive components and an additional MHC-sensitized allogeneic lymphocyte preparation step. Dependent claims further refine the medical framing and administration context.
In vitro co-culture priming for patient administration
An in vitro method comprising co-culturing target T cells from the patient to be treated, mature monocyte-derived dendritic cells from a first healthy donor, virus material or virus associated proteins or peptides, and lymphocytes from a second healthy donor sensitized against MHC class I and/or MHC class II antigens on antigen presenting cells (APCs) from the first healthy donor that are allogeneic with respect to the lymphocytes.
MHC-sensitized allogeneic lymphocytes from a mixed leukocyte reaction-derived preparation
The lymphocytes are obtained by culturing non-proliferating peripheral blood mononuclear cells (PBMCs) from the first healthy donor with PBMCs from the second healthy donor.
Medicament formulation for antiviral use
Antigen specific CD4+ and/or CD8+ T cells are used as a medicament.
Treatment or eliciting an anti-viral immunological response in a human
Antigen specific CD4+ and/or CD8+ T cells are used for treating a viral infection or eliciting an anti-viral immunological response in a human.
Administration together with a therapeutic viral vaccine
Administering antigen specific CD4+ and/or CD8+ T cells together with a therapeutic viral vaccine.
Administration after the first stimulation
Administering antigen specific CD4+ and/or CD8+ T cells after the first stimulation.
Overall claim coverage centers on an in vitro co-culture priming system using patient target T cells, mature monocyte-derived dendritic cells loaded with virus material or virus associated proteins or peptides, and MHC class I and/or MHC class II-sensitized allogeneic lymphocytes prepared from a non-proliferating PBMC culture between two healthy donors, with dependent claims specifying medicament/antiviral use and refinements such as combination with a therapeutic viral vaccine and timing after first stimulation.
Stated Advantages
Enhanced CD27+ CD8+ T-cell generation.
Reduced apoptosis (Annexin-V).
Increased proliferation.
Increased virus-specific CD8 frequencies after expansion/restimulation.
ASALs upregulate CD70 on DCs and increase IL-12, IFN-b3, and IL-2.
Documented Applications
Priming antigen specific CD4+ and/or CD8+ T cells for adoptive administration to a patient having a viral infection.
Virus-specific targeting including CMV, EBV, and influenza A peptide targets after expansion and restimulation.
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