Antibodies elicited by the first non-viral prophylactic cancer vaccine show tumor-specificity and immunotherapeutic potential

Sci Rep. 2016 Aug 22;6:31740. doi: 10.1038/srep31740.

Abstract

MUC1 is a shared tumor antigen expressed on >80% of human cancers. We completed the first prophylactic cancer vaccine clinical trial based on a non-viral antigen, MUC1, in healthy individuals at-risk for colon cancer. This trial provided a unique source of potentially effective and safe immunotherapeutic drugs, fully-human antibodies affinity-matured in a healthy host to a tumor antigen. We purified, cloned, and characterized 13 IgGs specific for several tumor-associated MUC1 epitopes with a wide range of binding affinities. These antibodies bind hypoglycosylated MUC1 on human cancer cell lines and tumor tissues but show no reactivity against fully-glycosylated MUC1 on normal cells and tissues. We found that several antibodies activate complement-mediated cytotoxicity and that T cells carrying chimeric antigen receptors with the antibody variable regions kill MUC1(+) target cells, express activation markers, and produce interferon gamma. Fully-human and tumor-specific, these antibodies are candidates for further testing and development as immunotherapeutic drugs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Antibodies / immunology*
  • Antibody Affinity / immunology
  • Base Sequence
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / therapeutic use
  • Cell Line
  • Cell Line, Tumor
  • Cytotoxicity, Immunologic / immunology
  • Epitopes / immunology
  • Female
  • HEK293 Cells
  • Humans
  • Immunoglobulin G / immunology
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • MCF-7 Cells
  • Male
  • Middle Aged
  • Mucin-1 / immunology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Young Adult

Substances

  • Antibodies
  • Cancer Vaccines
  • Epitopes
  • Immunoglobulin G
  • Mucin-1
  • Interferon-gamma