Targeting β2-microglobulin for induction of tumor apoptosis in human hematological malignancies

Jing Yang, Jianfei Qian, Michele Wezeman, Siqing Wang, Pei Lin, Michael Wang, Shmuel Yaccoby, Larry W. Kwak, Bart Barlogie, Qing Yi

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

We discovered that monoclonal antibodies (mAbs) specific to human β2-microglobulin (β2M) induce apoptosis in vitro and were therapeutic in mouse models of myeloma and other hematological tumor cells. Cell death occurred rapidly, without the need for exogenous immunological effector mechanisms. The mAbs induced cell death via recruiting MHC class I molecules to lipid rafts and activating Lyn and PLCγ2, leading to activated JNK and inhibited PI3K/Akt and ERK, compromised mitochondrial integrity, and caspase-9-dependent cascade activation. Although the expression of β2M on normal hematopoietic cells is a potential safety concern, the mAbs were selective to tumor-transformed cells and did not induce apoptosis of normal cells. Therefore, such mAbs offer the potential for a therapeutic approach to hematological malignancies.

Original languageEnglish (US)
Pages (from-to)295-307
Number of pages13
JournalCancer Cell
Volume10
Issue number4
DOIs
StatePublished - Oct 2006

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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