The bispecific anti-CD3 × anti-CD155 antibody mediates T cell immunotherapy for human prostate cancer

Invest New Drugs. 2019 Oct;37(5):810-817. doi: 10.1007/s10637-018-0683-9. Epub 2018 Oct 29.

Abstract

Expression of CD155 differs between tumor and normal tissues, and high expression of this molecule can promote tumor metastasis. Here, we investigate whether CD155 can serve as a target for T cell-mediated immunotherapy of human prostate cancer. We first demonstrate that prostate cancer cells, including PC-3, PC-3 M, and LNCAP cells, express CD155 at high levels. Next, the specific cytotoxic activity of activated T cells (ATCs) armed with a novel anti-CD3 × anti-CD155 bispecific antibody (CD155Bi-Ab) against tumor cells was evaluated by flow cytometry, lactate dehydrogenase assay (LDH), and ELISA. In contrast to unarmed ATCs, an increase in the cytotoxic activity of CD155Bi-armed ATCs against tumor cells was observed at an effector/target (E/T) ratio of 5:1. Moreover, CD155Bi-armed ATCs secreted more IFN-γ, TNF-α, and IL-2 and expressed higher levels of the activation marker CD69 than did unarmed ATCs. As CD155 Bi-Ab enhances the ability of ATCs to kill prostate cancer cells, CD155 is an effective target for cytotoxic T cells in human prostate cancer therapy.

Keywords: Bispecific antibody; CD155; Immunotherapy; Prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Bispecific / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • CD3 Complex / antagonists & inhibitors*
  • CD3 Complex / immunology
  • Cell Proliferation
  • Humans
  • Immunotherapy*
  • Lymphocyte Activation
  • Male
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy*
  • Receptors, Virus / antagonists & inhibitors*
  • Receptors, Virus / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Cells, Cultured

Substances

  • Antibodies, Bispecific
  • Antineoplastic Agents
  • CD3 Complex
  • Receptors, Virus
  • poliovirus receptor