MHC Multimers in Cancer Vaccines and Immune Monitoring

• US 20110318380A1
• Filed: 10/01/2009
• Published: 12/29/2011
• Est. Priority Date: 10/01/2008
• Status: Abandoned Application

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Dako Denmark A/S (Agilent Technologies, Inc.)
• Inventors: Brix, Liselotte, Schøller, Jørgen, Pedersen, Henrik
• Application Number:
  US13/122,027
• Publication Number:
  US 20110318380A1
• Time in Patent Office: Days
• US Class Current: 424/193.1
• CPC Class Codes: A61K 2239/31 characterized by the route of administration
• CPC Class Codes: A61K 2239/38 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2239/57 Skin; melanoma
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4615 Dendritic cells
• CPC Class Codes: A61K 39/4622 Antigen presenting cells
• CPC Class Codes: A61K 39/46445 Apoptosis related proteins, e.g. survivin or livin
• CPC Class Codes: A61K 47/6901 Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 14/70539 MHC-molecules, e.g. HLA-molecules
• CPC Class Codes: G01N 33/56972 White blood cells

Abstract

The present invention relates to MHC-peptide complexes and uses thereof in the diagnosis of, treatment of or vaccination against a disease in an individual. More specifically the invention discloses MHC complexes comprising cancer antigenic peptides and uses there of.

Claims

1. A MHC monomer comprising a-b-P or a MHC multimer comprising (a-b-P)_n, wherein n>

1,

wherein a and b together form a functional MHC protein capable of binding the antigenic peptide, P,

wherein (a-b-P) is the MHC-peptide complex formed when the peptide P binds to the functional MHC protein,

wherein each MHC peptide complex of a MHC multimer is associated with one or more multimerization domains and wherein P is a cancer antigenic peptide.

1631. A composition comprising a plurality of MHC monomers and/or MHC multimers and/or antigenic peptides and/or antigenic polypeptides according to any of claims 1 to 2, wherein the WIC monomers and/or MHC multimers and/or antigenic peptides and/or antigenic polypeptides are identical or different, and a carrier.

1632. A kit comprising a MHC monomer or a MHC multimer or an antigenic peptide or an antigenic polypeptide or a composition according to any of claims 1 to 2 and 1631 and at least one additional component, such as a positive control and/or instructions for use.

1633. A method for generating the MHC multimer according to claim 1, said method comprising the steps of

i) providing one or more antigenic peptides P;

ii) providing one or more functional MHC proteins,

iii) optionally providing one or more multimerization domains, and

iv) contacting or reacting the one or more antigenic peptides P and the one or more functional MHC proteins and the one or more multimerization domains simultaneously or sequentially in any order, thereby obtaining MHC multimers according to the present invention.

1634. A method for immune monitoring and/or diagnosing one or more diseases comprising the following steps

providing;

a MHC monomer or MHC multimer or antigenic peptide or antigenic polypeptide according to any of claims 1 to 2, or the individual components thereof, and

providing a population of T cells, and

measuring the number, activity or state of T cells specific for said MHC monomer, MHC multimer, antigenic peptide, antigenic polypeptide, and

thereby immune monitoring and/or diagnosing said one or more diseases.

1635. A method for isolation of one or more antigen-specific T cells, said method comprising the steps of

providing

a MHC monomer or MHC multimer or antigenic peptide or antigenic polypeptide according to any of claims 1 to 2 or individual components thereof,

providing a population of T cells, and

isolating T cells specific for said MFIC monomer, MHC multimer, antigenic peptide or antigenic polypeptide.

1636. A method for performing a vaccination of an individual in need thereof, said method comprising the steps of

providing

a MHC monomer or MHC multimer or antigenic peptide or antigenic polypeptide according to any of claims 1 to 2 or the individual components thereof, and

administering said MHC monomer, MHC multimer, antigenic peptide or antigenic polypeptide, to said individual and obtaining a protective immune response,

and thereby performing a vaccination of the said individual.

1637. A method for performing therapeutic treatment of an individual comprising the steps of

providing;

a MHC monomer or MHC multimer or antigenic peptide or an antigenic polypeptide according to any of claims 1 to 2 or the individual components thereof, and

isolating or obtaining T-cells from a source, such as an individual or an ex-vivo library or cell bank, wherein said isolated or obtained T-cells are specific for said provided MHC monomer, MHC multimer, antigenic peptide or antigenic polypeptide,

optionally manipulating said T-cells, and

introducing said isolated or obtained T-cells into an individual to be subjected to a therapeutic treatment, wherein the individual can be the same individual or a different individual from the source individual.

1638. A vaccine comprising:

one or more MHC monomers, one or more MHC multimers, one or more antigenic peptides or/and one or more antigenic polypeptides according to any of the claims 1 to 2 or one or more nucleic acids encoding said MHC monomers, MHC multimers, antigenic peptides and/or antigenic polypeptides.

1639. A method for performing a vaccination of an individual in need thereof, said method comprising the steps of

providing a vaccine according to claim 1638

administering said vaccine to said individual and obtaining a protective immune response and thereby performing a vaccination of the said individual.

1640. A kit comprising a vaccine according to claim 1638 and at least one additional component.

1641. A method for minimization of undesired binding of the MHC multimer according to claim 1.

2. An antigenic peptide comprising or consisting of a sequence selected from the group of sequences included in FIG. 29 and FIG. 32 and modified sequences obtained by modification of a sequence selected from the group of sequences included in FIG. 29 and FIG. 32.

3-1630. -1630. (canceled)

1642. A method for performing a control experiment comprising use of MHC multimers as a positive control.

1643. A method for performing a control experiment comprising use of MHC multimers as a negative control.