Immunogenic muc1 glycopeptides
OwnerFranz-Georg Hanischinventor
Life of this patent
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Abstract
Provided are novel MUC1 peptides for use in anti-tumor vaccination and methods of producing those peptides. Furthermore, methods of producing a population of autologous antigen presenting cells (APCs) and of producing genetically engineered APCs, which are capable of inducing effective immune responses against MUC1 are described. The described peptides are particularly useful for the treatment of breast cancer or other MUC1-positive carcinomas including colorectal, pancreatic and gastric carcinomas.
Claims50
A peptide of least 9 amino acids in length derived from the tandem repeat domain of MUC1 and having the amino acid sequence SAP at its N-terminus.
7-24. (canceled)
A method of producing a peptide having at least 9 amino acids derived from the tandem repeat domain of MUC1 and having the amino acid sequence SAP at its N-terminus, comprising the following steps:
- (a) providing a peptide comprising the tandem repeat domain of MUC1 or a part thereof, which part at least contains one repeating unit of said tandem repeat domain of MUC1;
- (b) contacting the peptide of (a) with an effective amount of cathepsin-L or a closely related enzyme hereof, thereby cleaving the peptide;
- and
- (c) isolating the fragments produced in (b).
An ex vivo-method of producing a population of autologous antigen presenting cells (APCs), which are capable of inducing effective immune responses against MUC1, comprising the steps of
- (a) providing autologous APCs from a tumor patient;
- (b) contacting the autologous APCs from the tumor patient with an effective amount of a peptide or fusion molecule comprising at least 9 amino acids of the tandem repeat domain of MUC1 and having the amino acid sequence SAP at its N-terminus, wherein said contacting is under conditions which allow endocytosis, processing, and MHC class II presentation of fragments of said peptide or fusion molecule by said APCs;
- and
- (c) isolating said peptide or fusion molecule fragment-presenting APCs for the purpose of immunotherapeutic application in the patient.
The method of 33, wherein one or more threonines or serines of said peptide or fusion molecule are O-glycosylated.
An ex vivo-method of producing genetically engineered antigen presenting cells (APCs), which are capable of inducing effective immune responses against MUC1, comprising the steps of
- (a) providing a nucleic acid encoding a peptide or fusion molecule comprising at least 9 amino acids of the tandem repeat domain of MUC1 and having the amino acid sequence SAP at its N-terminus,
- (b) transfecting the APCs with said nucleic acid, and
- (c) selecting APCs, which present said peptides in an MHC II restricted manner.
The method of 41, wherein one or more threonines or serines of said peptide are O-glycosylated.
A composition comprising a therapeutically effective amount of a peptide or fusion molecule comprising at least 9 amino acids of the tandem repeat domain of MUC1 add having the amino acid sequence SAP at its N-terminus or an antigen presenting cell comprising said peptide or fusion molecule and a pharmaceutically acceptable carrier.
The composition of 51, wherein one or more threonines or serines of said peptide or fusion molecule are O-glycosylated.
A method of treating a patient suffering from a MUC1-positive carcinoma, said method comprising administering a composition comprising a peptide or fusion molecule comprising at least 9 amino acids of the tandem repeat domain of MUC1 and having the amino acid sequence SAP at its N-terminus or an antigen presenting cell comprising said peptide or fusion molecule, wherein said composition is administered to said patient in an amount effective to induce an immune response against MUC1.
The method of 59, wherein one or more threonines or serines of said peptide or fusion molecule are O-glycosylated.
Dependencies are inferred from the claim text.