Killing tumor cells through their surface beta(2)-microglobulin or major histocompatibility complex class I molecules
- PMID: 20143445
- PMCID: PMC2847067
- DOI: 10.1002/cncr.24953
Killing tumor cells through their surface beta(2)-microglobulin or major histocompatibility complex class I molecules
Abstract
Targeted antibody-based therapy has been used successfully to treat cancers. Recent studies have demonstrated that tumor cells treated with antibodies specific for beta(2)-microglobulin (beta(2)M) or major histocompatibility complex (MHC) class I molecules undergo apoptosis in vitro and in vivo (mouse models). Antibodies against beta(2)M 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-gamma2-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 beta(2)M 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 beta(2)M or MHC class I by using antibodies or other agents offers a potential therapeutic approach for beta(2)M/MHC class I-expressing malignancies. Cancer 2010. (c) 2010 American Cancer Society.
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References
-
- Yewdell JW, Reits E, Neefjes J. Making sense of mass destruction: quantitating MHC class I antigen presentation. Nat Rev Immunol. 2003;3:952–961. - PubMed
-
- Buus S. MHC restricted antigen presentation and T cell recognition. Dan Med Bull. 1994;41:345–358. - PubMed
-
- Bjorkman PJ, Burmeister WP. Structures of two classes of MHC molecules elucidated: crucial differences and similarities. Curr Opin Struct Biol. 1994;4:852–856. - PubMed
-
- Strominger JL. Human histocompatibility proteins. Immunol Rev. 2002;185:69–77. - PubMed
-
- Natarajan K, Li H, Mariuzza RA, et al. MHC class I molecules, structure and function. Rev Immunogenet. 1999;1:32–146. - PubMed
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