BCR-ABL imatinib resistance-associated peptides and methods of use thereof
OwnerDavid Scheinberg, Javier Pinilla-Ibarzinventors
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Abstract
The present invention is directed to immunogenic peptides, compositions and vaccines comprising same, and methods of use thereof for treating, inhibiting or reducing the incidence of a cancer associated with an activated kinase, and methods of generating a heteroclitic immune response against, or cytotoxic T cells specifically recognizing cancer cells which are associated with an activated kinase.
Claims53
An isolated bcr-abl peptide comprising a kinase inhibitor-induced mutation, wherein said isolated bcr-abl peptide binds to an MHC class I molecule.
A method of treating a subject with a cancer associated with an activated kinase, wherein a cell of said cancer presents on an MHC class I molecule thereof a peptide antigen comprising a heteroclitic peptide, the method comprising administering to said subject said heteroclitic peptide, wherein
- said heteroclitic peptide contains a first mutation, said first mutation occurring in said cancer, and
- said heteroclitic peptide further comprises an additional mutation that increases a binding to said MHC class I molecule,
- whereby said heteroclitic peptide stimulates an immune response to said cell of said cancer, thereby treating a subject with a cancer associated with an activated kinase.
A method of reducing an incidence or a relapse of a cancer associated with an activated kinase in a subject, wherein a cell of said cancer presents on an MHC class I molecule thereof a peptide antigen comprising a heteroclitic peptide, the method comprising administering to said subject said heteroclitic peptide, wherein
- said heteroclitic peptide contains a first mutation, said first mutation occurring in said cancer, and
- said heteroclitic peptide further comprises an additional mutation that increases a binding said MHC class I molecule,
- whereby said heteroclitic peptide stimulates an immune response to said cell of said cancer, thereby reducing an incidence or a relapse of a cancer associated with an activated kinase in a subject.
A method of stimulating cytotoxic T lymphocytes (CTL) specific for a cancer cell expressing an activated kinase, wherein said cancer cell presents on an MHC class I molecule thereof a peptide antigen comprising a heteroclitic peptide, the method comprising contacting a lymphocyte population with an antigen presenting cell (APC), wherein
- said APC is associated with said heteroclitic peptide;
- said heteroclitic peptide contains a first mutation, said first mutation occurring in said cancer;
- and
- said heteroclitic peptide further comprises an additional mutation that increases a binding to said MHC class I molecule,
- thereby stimulating CTL specific for a cancer cell expressing an activated kinase.
An isolated bcr-abl peptide, having an amino acid sequence corresponding to a sequence selected from SEQ ID No:
- 1-12.
Dependencies are inferred from the claim text.