Induction of tumor-specific T cell immunity by anti-DR5 antibody therapy

J Exp Med. 2004 Feb 16;199(4):437-48. doi: 10.1084/jem.20031457. Epub 2004 Feb 9.

Abstract

Because tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) preferentially induces apoptosis in tumor cells and plays a critical role in tumor surveillance, its receptor is an attractive target for antibody-mediated tumor therapy. Here we report that a monoclonal antibody (mAb) against the mouse TRAIL receptor, DR5, exhibited potent antitumor effects against TRAIL-sensitive tumor cells in vivo by recruiting Fc receptor-expressing innate immune cells, with no apparent systemic toxicity. Administration of the agonistic anti-DR5 mAb also significantly inhibited experimental and spontaneous tumor metastases. Notably, the anti-DR5 mAb-mediated tumor rejection by innate immune cells efficiently evoked tumor-specific T cell immunity that could also eradicate TRAIL-resistant variants. These results suggested that the antibody-based therapy targeting DR5 is an efficient strategy not only to eliminate TRAIL-sensitive tumor cells, but also to induce tumor-specific T cell memory that affords a long-term protection from tumor recurrence.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Apoptosis Regulatory Proteins
  • Aspartate Aminotransferases / blood
  • Immunity, Cellular / immunology
  • Immunotherapy / methods
  • Mammary Neoplasms, Animal / immunology
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Receptors, Fc / immunology
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor / immunology*
  • T-Lymphocytes / immunology*
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha / deficiency
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Apoptosis Regulatory Proteins
  • Membrane Glycoproteins
  • Receptors, Fc
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor
  • TNF-Related Apoptosis-Inducing Ligand
  • Tnfrsf10b protein, mouse
  • Tnfsf10 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Aspartate Aminotransferases
  • Alanine Transaminase