title: Adoptive immunotherapy of lung cancer with immobilized anti-TCRgammadelta antibody-expanded human gammadelta T-cells in peripheral blood.
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.
authors.affiliation: Department of Immunology, School of Basic Medicine, Peking Union Medical College, and Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Kang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhou
authors.forename: Tie
authors.initials: T
authors.lastname: Zhang
authors.forename: Lifang
authors.initials: L
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Lu
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.forename: Lianxian
authors.initials: L
authors.lastname: Cui
authors.forename: Wei
authors.initials: W
authors.lastname: He
mesh_terms: D000328:Adult; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D011379:Prognosis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000906:Antibodies; D016692:Receptors, Antigen, T-Cell, gamma-delta