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New strategy for cancer biotherapy: Combining usage of molecular targeted agents and adoptive cellular immunotherapy
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Abstract:
As a promising new strategy for cancer biotherapy, combined therapy of molecular targeted agents and adoptive cellular immunotherapy is established based on the biological characteristics of NK cell activating signal pathway (natural killer group 2 member Dnatural killer group 2 member D ligand, NKG2DNKG2DLs), especially its regulable ligand and receptor theory. Molecular targeted agents play dual functions: in addition to their toxic effects against tumor cells, they can also induce expression of NKG2D ligands on tumor cells, resulting in enhanced immune eradication of NK cells. As a pivotal activating receptor for NK cells, NKG2D and its ligands play important roles in the antitumor immune system, especially adoptive cellmediated immune response. NKG2D is mainly expressed by NK cells, CD8+T cells, γδ T cells and activated macrophages. As for NKG2D ligands, they have restricted expressions in normal tissues, but are frequently expressed on primary tumors. Therefore, expressions of these ligands are closely related to the antitumor effect of immune cells, without damage to the normal tissues. NKG2D ligands can be regulated by multiple stimuli including molecular targeted agents. The immunoregulation induced by molecular targeted agents through NKG2DNKG2DLs pathway has been shown valuable both for its distinguished targeting effects and for its wellestablished regulating effects. In summary, combination of molecular targeted agents and adoptive cellular immunotherapy may represent a bright future for tumor biotherapy.
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Project Supported:
Project supported by the National Natural Science Foundation of China (No. 30973454), and the Key Program of Natural Science Foundation of Guangdong Province (No. 9251051501000007)
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