Adoptive immunotherapy of lung cancer with immobilized anti-TCRγδ antibody-expanded human γδ T-cells in peripheral blood

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.