Details

Autor(en) / Beteiligte

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

Titel

Targeting β 2-microglobulin for induction of tumor apoptosis in human hematological malignancies

Ist Teil von

• Cancer cell, 2006, Vol.10 (4), p.295-307

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2006

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• We discovered that monoclonal antibodies (mAbs) specific to human β 2-microglobulin (β 2M) 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 β 2M 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.