Abstract |
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 gammadelta T-cells in peripheral blood and tumor infiltrating T lymphocytes with immobilized anti-TCRgammadelta antibody. Such expanded gammadelta T-cells exhibited potent cytolytic activity to different tumor cell lines in vitro and in vivo. Here we further characterized human anti-TCRgammadelta-expanded gammadelta T-cells and tested their antitumor function in treatment for lung cancer in nude mice. In comparison to gammadelta T-cells activated by phosphoantigen, a prevalent Vdelta2 stimulus, anti-TCRgammadelta-expanded gammadelta T-cells had similar major subset with Vdelta2 phenotype, but they had about 10% of Vdelta1 subsets and high percentages of CD27(-)CD45RA(-) and CD27(-)CD45RA(+) effector cells. They also displayed TCR diversity of multiple clones. Importantly, the antibody-expanded gammadelta 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-TCRgammadelta-expanded gammadelta T-cells prolonged tumor bearing mouse survival and slowed down tumor growth, with similar efficacy to chemotherapy by cis-platinum. Moreover, adoptively transferred human gammadelta T-cells survived for more than one month in vivo. Finally, gammadelta T-cells derived from 11 cases of patients with lung cancer had proliferative activity after TCRgammadelta 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, TNFalpha and IFNgamma. Taken together, our finding suggests that anti-TCRgammadelta expanded gammadelta T-cells may be used as cellular therapy in treatment of lung cancer.
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Authors | Ning Kang, Jianhua Zhou, Tie Zhang, Lifang Wang, Fang Lu, Ying Cui, Lianxian Cui, Wei He |
Journal | Cancer biology & therapy
(Cancer Biol Ther)
Vol. 8
Issue 16
Pg. 1540-9
(Aug 2009)
ISSN: 1555-8576 [Electronic] United States |
PMID | 19471115
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies
- Receptors, Antigen, T-Cell, gamma-delta
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Topics |
- Adult
- Animals
- Antibodies
(immunology, pharmacology)
- Cell Line, Tumor
- Female
- Humans
- Immunotherapy, Adoptive
(methods)
- Lung Neoplasms
(blood, genetics, immunology, therapy)
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Middle Aged
- Prognosis
- Receptors, Antigen, T-Cell, gamma-delta
(genetics, immunology)
- T-Lymphocytes
(immunology)
- Xenograft Model Antitumor Assays
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