Adoptive immunotherapy of lung cancer with immobilized anti-TCRgammadelta antibody-expanded human gammadelta 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 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.
Kang
Ning
N
Department of Immunology, School of Basic Medicine, Peking Union Medical College, and Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.
Zhou
Jianhua
J
Zhang
Tie
T
Wang
Lifang
L
Lu
Fang
F
Cui
Ying
Y
Cui
Lianxian
L
He
Wei
W
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
D000906:Antibodies; D016692:Receptors, Antigen, T-Cell, gamma-delta