Journal
CANCER BIOLOGY & THERAPY
Volume 8, Issue 16, Pages 1540-1549Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cbt.8.16.8950
Keywords
gamma delta T-cells; adoptive immunotherapy; ex vivo cell expansion; TCR ligandation; lung cancer; tumor treatment; preclinical study
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Funding
- National High Technology Research and Development of China [2006AA02Z480, 2007AA021109]
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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 gamma delta T-cells in peripheral blood and tumor infiltrating T lymphocytes with immobilized anti-TCR gamma delta antibody. Such expanded gamma delta T-cells exhibited potent cytolytic activity to different tumor cell lines in vitro and in vivo. Here we further characterized human anti-TCR gamma delta-expanded gamma delta T-cells and tested their antitumor function in treatment for lung cancer in nude mice. In comparison to gamma delta T-cells activated by phosphoantigen, a prevalent V delta 2 stimulus, anti-TCR gamma delta-expanded gamma delta T-cells had similar major subset with V delta 2 phenotype, but they had about 10% of V delta 1 subsets and high percentages of CD27(-)CD45RA(-) and CD27(-)CD45RA(+) effector cells. They also displayed TCR diversity of multiple clones. Importantly, the antibody-expanded gamma delta 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-TCR gamma delta-expanded gamma delta T-cells prolonged tumor bearing mouse survival and slowed down tumor growth, with similar efficacy to chemotherapy by cis-platinum. Moreover, adoptively transferred human gamma delta T-cells survived for more than one month in vivo. Finally, gamma delta T-cells derived from 11 cases of patients with lung cancer had proliferative activity after TCR gamma delta 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, TNF alpha and IFN gamma. Taken together, our finding suggests that anti-TCR gamma delta expanded gamma delta T-cells may be used as cellular therapy in treatment of lung cancer.
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