Lung cancer is the leading cause of cancer death. The prognosis of metastatic lung cancer is poor. We had previously established the condition to expand human γδ T-cells in peripheral blood and tumor infiltrating T lymphocytes with immobilized anti-TCRγδ antibody. Such expanded γδ T-cells exhibited potent cytolytic activity to different tumor cell lines in vitro and in vivo. Here we further characterized human anti-TCRγδ-expanded γδ T-cells and tested their antitumor function in treatment for lung cancer in nude mice. In comparison to γδ T-cells activated by phosphoantigen, a prevalent Vδ2 stimulus, anti-TCRγδ-expanded γδ T-cells had similar major subset with Vδ2 phenotype, but they had about 10% of Vδ1 subsets and high percentages of CD27 -CD45RA -and CD27 -CD45RA + effector cells. They also displayed TCR diversity of multiple clones. Importantly, the antibody-expanded γδ T-cells showed strong cytotoxicity to three lung cancer cell lines and had significant antitumor effect on squamous lung carcinoma in nude mice. The ex vivo anti-TCRγδ-expanded γδ T-cells prolonged tumor bearing mouse survival and slowed down tumor growth, with similar efficacy to chemotherapy by cis-platinum. Moreover, adoptively transferred human γδ T-cells survived for more than one month in vivo. Finally, γδ T-cells derived from 11 cases of patients with lung cancer had proliferative activity after TCRγδ ligandation, displayed marked cytotoxicity to lung cancer cells and expressed cytotoxicity-or antitumor activity-related molecules, such as perforin, granzyme A and B, Fas ligand, TNFα and IFNγ. Taken together, our finding suggests that anti-TCRγδ expanded γδ T-cells may be used as cellular therapy in treatment of lung cancer.
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