Killing tumor cells through their surface β2-microglobulin or major histocompatibility complex class I molecules

Research output: Contribution to journalReview article

23 Scopus citations

Abstract

Targeted antibody-based therapy has been used successfully to treat cancers. Recent studies have demonstrated that tumor cells treated with antibodies specific for β2-microglobulin (b2M) or major histocompatibility complex (MHC) class I molecules undergo apoptosis in vitro and in vivo (mouse models). Antibodies against β2M or MHC class I induce tumor cell apoptosis by 1) recruiting MHC class I molecules to lipid rafts and activating LYN kinase and the signal-transducing enzyme phospholipase C-γ2-dependent c-Jun N-terminal kinase signaling pathway and 2) expelling interleukin 6 and insulin-like growth factor 1 receptors out of lipid rafts and inhibiting the growth and survival factor-induced activation of the phosphatidylinositol 3-kinase/Akt and extracellular signal-related kinase pathways. Consequently, mitochondrial integrity is compromised, and the caspase-9-dependent cascade is activated in treated tumor cells. However, although β2M and MHC class I are expressed on normal hematopoietic cells, which is a potential safety concern, the monoclonal antibodies were selective to tumor cells and did not damage normal cells in vitro or in human-like mouse models. These findings suggest that targeting β2M or MHC class I by using antibodies or other agents offers a potential therapeutic approach for β2M/MHC class I-expressing malignancies.

Original languageEnglish (US)
Pages (from-to)1638-1645
Number of pages8
JournalCancer
Volume116
Issue number7
DOIs
StatePublished - Apr 1 2010

Keywords

  • Major histocompatibility complex class I
  • Monoclonal antibodies
  • Signaling pathways
  • Tumor cell apoptosis
  • β-microglobulin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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