Adoptive immunotherapy using specific cytotoxic T lymphocytes against human lung-cancer-engrafted severe combined immunodeficiency mice.
OBJECTIVE
We studied the ability of human lung-cancer-specific cytotoxic T lymphocytes to suppress the growth of human lung adenocarcinoma (PC-9) engrafted in severe combined immunodeficiency mice.


METHODS
PC-9-specific cytotoxic T lymphocytes were generated by multiple stimulation with irradiated PC-9 cells of regional lymph node lymphocytes from lung cancer patients expressing the same human leukocyte antigen-A locus haplotype as PC-9 following expansion due to the administration of immobilized anti cluster of differentiation 3 mAb and interleukin-2. Cytotoxic T lymphocytes showed specific cytotoxicity against PC-9 cells in vitro. Severe combined immunodeficiency mice with a subcutaneous graft of PC-9 were treated with a PC-9-specific cytotoxic T lymphocyte by i.v. injection and/or with interleukin-2 by s.c. injection.


RESULTS
Cytotoxic T lymphocyte treatment suppressed PC-9 graft growth significantly an effect, significantly enhanced when combined with interleukin-2 injection. To evaluate the in vivo specificity of anti-PC-9 cytotoxic T lymphocytes, each mouse was subcutaneously inoculated in the right flank with PC-9, and in the left flank with A549 or Sq-1. Cytotoxic T lymphocytes plus interleukin-2 treatment was found to suppress PC-9 growth selectively, but not A549 or Sq-1 growth.


CONCLUSIONS
These results provide sufficient rationale for conducting further clinical trials on immunotherapy using cytotoxic T lymphocyte for lung cancer patients.
Imahayashi
S
S
Department of Surgery II, Faculty of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Yoshino
I
I
Eifuku
R
R
Takenoyama
M
M
Hanagiri
T
T
Yasumoto
K
K
D000230:Adenocarcinoma / Q000276:immunology* / Q000628:therapy; D000818:Animals; D016219:Immunotherapy, Adoptive; D008175:Lung Neoplasms / Q000276:immunology* / Q000628:therapy; D008297:Male; D051379:Mice; D016513:Mice, SCID; D016511:Severe Combined Immunodeficiency / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*