Adoptive immunotherapy for advanced cancer patients using in vitro activated cytotoxic T lymphocytes.
OBJECTIVE
We evaluated the clinical efficacy of adoptive immunotherapy using in vitro activated cytotoxic T lymphocytes (CTL) in the treatment of patients with advanced cancer.


METHODS
CTL were induced with the mixed lymphocyte and tumor cell culture method, in which lymphocytes isolated from patient peripheral blood mononuclear cells were mixed with inactivated autologous tumor cells. Activated lymphocytes were administered intravenously to 11 patients once every 2 weeks for 10 weeks (i.e., 5 doses).


RESULTS
Tumor reduction and decreased tumor marker were observed in 4 patients. Notably, successful CTL induction was identified in all of these patients. In patients who did not show induction of CTL response, a decreased proportion of lymphocytes, especially CD8(+) cells, and increased levels of CD14(+) cells were frequently observed. Fluorescence-activated cell sorter analysis indicated that expression of HLA class I and costimulatory factor B7-1 molecules was diminished on tumor cells. This was partly recovered with interferon-gamma, which resulted in successful induction of a CTL response.


CONCLUSIONS
It was suggested that in vitro CTL induction is difficult in patients with advanced cancer. However, once the cells were induced successfully, some favorable clinical effects were seen by the adoptive transfer of such cell populations.
Soda
H
H
First Department of Surgery, Chiba University School of Medicine, Chiba City, Japan. hsouda@chiba-cc.pref.chiba.jp
Koda
K
K
Yasutomi
J
J
Oda
K
K
Takiguchi
N
N
Saito
N
N
Nakajima
N
N
D000368:Aged; D001859:Bone Neoplasms / Q000556:secondary; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D007694:Killer Cells, Natural / Q000276:immunology; D018950:Lipopolysaccharide Receptors; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D010534:Peritoneal Neoplasms / Q000556:secondary; D013602:T-Lymphocytes, Cytotoxic / Q000637:transplantation*; D014407:Tumor Cells, Cultured
D018950:Lipopolysaccharide Receptors