A novel bispecific antibody, BiSS, with potent anti-cancer activities

Cancer Biol Ther. 2016 Apr 2;17(4):364-70. doi: 10.1080/15384047.2016.1139266. Epub 2016 Feb 1.

Abstract

One of the most active fields in cancer immunotherapy is the study of bispecific antibodies, which engage immune cells to kill cancer cells. However, a variety of issues are associated with most of current bispecific antibody formats. In this study, we present a novel bispecific antibody, BiSS (Bispecific antibody with Single domain, Single domain antibodies), which was constructed by linking 2 single domain antibodies, anti-CEA and anti-CD16, in tandem. Unlike most other bispecific antibodies, the BiSS antibody can be expressed and purified from E.coli in large quantities. By recruiting natural killer cells (NK cells) to CEA-positive cancer cells, BiSS led to cancer cell death in vitro. In xenograft models, the BiSS protein blocked cancer progression. The data suggested that the single domain-based bispecific antibody BiSS was functional and can be potentially applied to a broad range of immunotherapies.

Keywords: Bacterial expression; BiSS; CD16; CEA; bispecific antibody; natural killer cells; single domain antibody.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bispecific / metabolism*
  • Cell Line, Tumor
  • Humans
  • Immunotherapy / methods*
  • Killer Cells, Natural / metabolism*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Bispecific