Methods for treating breast cancer and for identifying breast cancer antigens

Inventors

Han, David • Qendro, Veneta

Assignees

University of Connecticut

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Publication Number

US-12461110-B2

Patent

Publication Date

2025-11-04

Expiration Date


Abstract

Disclosed herein are isolated compositions including at least 2 of mutant peptides selected from the group consisting of SEQ ID NOS: 1-149, or polypeptides comprising the mutant peptides; wherein the composition comprises mutant peptides encoded by 2 or more genes. Also disclosed are methods for personalized treatment of breast cancer involving creating a peptide array of mutant peptides comprising the mutations in protein-encoding regions of the high-frequency cancer genes or the exome in a subject and screening the peptide array with a biological sample from the subject to detect antibodies in the biological sample that bind to the array, to detect antigenic targets for therapy in treating the subject.

Core Innovation

The invention relates to isolated compositions comprising mutant peptides and/or polypeptides that include mutant peptides, where the mutant peptides are selected from SEQ ID NOS: 1-82, 84-91, and 93-149, and wherein the mutant peptides are encoded by 10 or more genes. In some embodiments, the compositions further include wild-type counterparts of the mutant peptides for determining antibody binding specificity relevant to breast cancer treatment.

One core aspect is a method for identifying antigenic targets for breast cancer treatment by contacting a peptide array with a biological sample from a subject having breast cancer. The peptide array comprises at least 25 mutant peptides selected from the specified SEQ ID NOS or polypeptides comprising those mutant peptides, includes mutant peptides encoded by 10 or more genes, and further comprises mutant peptides that are fluorescently labeled.

Another core aspect is a method for monitoring breast cancer immunotherapy by contacting a biological sample from a subject undergoing or having undergone breast cancer immunotherapy with an isolated composition comprising at least 25 mutant peptides or polypeptides comprising the mutant peptides encoded by 10 or more genes. The method determines an amount of antibodies against the mutant peptides in the bodily fluid sample, and an increase in the amount of antibodies relative to a control indicates efficacy, while a decrease or no increase relative to a control indicates ineffectiveness.

Claims Coverage

The independent claims are directed to two core methods. Across the independent claims, the inventive features center on specified mutant-peptide sets, array or composition scale, encoding by 10 or more genes, antibody binding or detection, wild-type counterparts, fluorescent labeling, and efficacy determination using increase versus decrease or no increase relative to a control.

Fluorescently labeled mutant-peptide array with wild-type counterparts for antigen identification

A method contacting a peptide array with a biological sample from a subject having breast cancer, where the peptide array comprises at least 25 mutant peptides selected from SEQ ID NOS: 1-82, 84-91, and 93-149 or polypeptides comprising the mutant peptides, the array comprises mutant peptides encoded by 10 or more genes, and the mutant peptides are fluorescently labeled; detecting binding of antibodies in the serum to the mutant peptides and the wild-type counterparts thereof to identify antigenic targets for therapy.

Antibody monitoring against mutant peptides relative to control to assess immunotherapy efficacy

A method monitoring breast cancer immunotherapy by contacting a biological sample from a subject undergoing or has undergone breast cancer immunotherapy with an isolated composition comprising at least 25 mutant peptides selected from SEQ ID NOS: 1-82, 84-91, and 93-149 or polypeptides comprising the mutant peptides, where the composition comprises mutant peptides encoded by 10 or more genes; determining an amount of antibodies against the mutant peptides in the bodily fluid sample, wherein an increase in the amount of antibodies relative to a control indicates efficacy and wherein a decrease or no increase relative to a control indicates ineffectiveness.

Collectively, the claims cover identifying breast cancer antigenic targets by serum antibody binding to a fluorescently labeled peptide array containing at least 25 specified mutant peptides encoded by 10 or more genes and their wild-type counterparts, and monitoring breast cancer immunotherapy by measuring antibody amounts against those mutant peptides in bodily fluid samples, where the direction of change relative to a control indicates efficacy or ineffectiveness.

Stated Advantages

An increase in the amount of antibodies relative to a control indicates efficacy of the breast cancer immunotherapy in the subject.

A decrease or no increase in the amount of antibodies relative to a control indicates that the immunotherapy is ineffective in the subject.

Documented Applications

Identifying antigenic targets for breast cancer treatment by contacting a fluorescently labeled mutant-peptide array with a subject’s serum and detecting antibody binding to mutant peptides and wild-type counterparts.

Monitoring breast cancer immunotherapy efficacy or ineffectiveness in a subject by contacting a bodily fluid sample with an isolated composition of mutant peptides and determining antibody amounts relative to a control.

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