Identification of anti-CA125 antibody responses in ovarian cancer patients by a novel deep sequence-coupled biopanning platform

Kathryn M. Frietze, Richard B.S. Roden, Ji Hyun Lee, Yang Shi, David S. Peabody, Bryce Chackerian

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

High-grade epithelial ovarian cancer kills more women than any other gynecologic cancer and is rarely diagnosed at an early stage. We sought to identify tumor-associated antigens (TAA) as candidate diagnostic and/or immunotherapeutic targets by taking advantage of tumor autoantibody responses in individuals with ovarian cancer. Plasma-derived IgG from a pool of five patients with advanced ovarian cancer was subjected to iterative biopanning using a library of bacteriophage MS2 viruslike particles (MS2-VLPs) displaying diverse short random peptides. After two rounds of biopanning, we analyzed the selectant population of MS2-VLPs by Ion Torrent deep sequencing. One of the top 25 most abundant peptides identified (DISGTNTSRA) had sequence similarity to cancer antigen 125 (CA125/MUC16), a well-known ovarian cancer-associated antigen. Mice immunized with MS2-DISGTNTSRA generated antibodies that cross-reacted with purified soluble CA125 from ovarian cancer cells but not membrane-bound CA125, indicating that the DISGTNTSRA peptide was a CA125/MUC16 peptide mimic of soluble CA125. Preoperative ovarian cancer patient plasma (n = 100) was assessed for anti-DISGTNTSRA, anti-CA125, and CA125. Patients with normal CA125 (<35 IU/mL) at the time of diagnosis had significantly more antibodies to DISGTNTSRA and to CA125 than those patients who had high CA125 (>35 IU/mL). A statistically significant survival advantage was observed for patients who had either normal CA125 and/or higher concentrations of antibodies to CA125 at the time of diagnosis. These data show the feasibility of using deep sequence-coupled biopanning to identify TAA autoantibody responses from cancer patient plasma and suggest a possible antibody-mediated mechanism for low CA125 plasma concentrations in some ovarian cancer patients.

Original languageEnglish (US)
Pages (from-to)157-164
Number of pages8
JournalCancer Immunology Research
Volume4
Issue number2
DOIs
StatePublished - Feb 2016

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Ovarian Neoplasms
Antibody Formation
Anti-Idiotypic Antibodies
Peptides
Neoplasm Antigens
Autoantibodies
Antibodies
Neoplasms
CA-125 Antigen
Levivirus
High-Throughput Nucleotide Sequencing
Immunoglobulin G
Cell Membrane
Ions
Antigens
Survival
Population

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

Cite this

Identification of anti-CA125 antibody responses in ovarian cancer patients by a novel deep sequence-coupled biopanning platform. / Frietze, Kathryn M.; Roden, Richard B.S.; Lee, Ji Hyun; Shi, Yang; Peabody, David S.; Chackerian, Bryce.

In: Cancer Immunology Research, Vol. 4, No. 2, 02.2016, p. 157-164.

Research output: Contribution to journalArticle

Frietze, Kathryn M. ; Roden, Richard B.S. ; Lee, Ji Hyun ; Shi, Yang ; Peabody, David S. ; Chackerian, Bryce. / Identification of anti-CA125 antibody responses in ovarian cancer patients by a novel deep sequence-coupled biopanning platform. In: Cancer Immunology Research. 2016 ; Vol. 4, No. 2. pp. 157-164.
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abstract = "High-grade epithelial ovarian cancer kills more women than any other gynecologic cancer and is rarely diagnosed at an early stage. We sought to identify tumor-associated antigens (TAA) as candidate diagnostic and/or immunotherapeutic targets by taking advantage of tumor autoantibody responses in individuals with ovarian cancer. Plasma-derived IgG from a pool of five patients with advanced ovarian cancer was subjected to iterative biopanning using a library of bacteriophage MS2 viruslike particles (MS2-VLPs) displaying diverse short random peptides. After two rounds of biopanning, we analyzed the selectant population of MS2-VLPs by Ion Torrent deep sequencing. One of the top 25 most abundant peptides identified (DISGTNTSRA) had sequence similarity to cancer antigen 125 (CA125/MUC16), a well-known ovarian cancer-associated antigen. Mice immunized with MS2-DISGTNTSRA generated antibodies that cross-reacted with purified soluble CA125 from ovarian cancer cells but not membrane-bound CA125, indicating that the DISGTNTSRA peptide was a CA125/MUC16 peptide mimic of soluble CA125. Preoperative ovarian cancer patient plasma (n = 100) was assessed for anti-DISGTNTSRA, anti-CA125, and CA125. Patients with normal CA125 (<35 IU/mL) at the time of diagnosis had significantly more antibodies to DISGTNTSRA and to CA125 than those patients who had high CA125 (>35 IU/mL). A statistically significant survival advantage was observed for patients who had either normal CA125 and/or higher concentrations of antibodies to CA125 at the time of diagnosis. These data show the feasibility of using deep sequence-coupled biopanning to identify TAA autoantibody responses from cancer patient plasma and suggest a possible antibody-mediated mechanism for low CA125 plasma concentrations in some ovarian cancer patients.",
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