Tumoricidal effect of human PBMC following stimulation with OK-432 and its application for locoregional immunotherapy in head and neck cancer patients.
Both cell-mediated and cytokine-mediated antitumor activities were induced in peripheral blood mononuclear cells (PBMC) in short-term culture with streptococcal preparation, OK-432. Kinetic analysis of OK-432-activated killer activity (OKAK) showed that it reached a plateau level much faster (by 48 h of culture) than that detected in PBMC stimulated with recombinant interleukin 2 (rIL-2) (lymphokine-activated killer: LAK). We also found that the tumor growth inhibitory factor (TGIF) activity was produced in the culture supernatant (CSN) of the OK-432-activated PBMC (OK-MC) and the activity synchronously increased with augmentation of OKAK activity. The TGIF activity was rarely found in the CSN of rIL-2-stimulated PBMC. The TGIF activity detected in CSN of OK-MC was further characterized as derived from a cytokine different from interferon gamma (IFN gamma), tumor necrosis factor (TNF), or lymphotoxin (LT) by a neutralization test using monoclonal antibodies to these cytokines. These 48-h-cultured-OK-MC were adoptively transferred (adoptive immunotherapy: AIT) into 19 head and neck cancer patients either alone or in combination with chemotherapy and/or radiation therapy, and their therapeutic effects were examined. AIT was performed by intra-arterial or intratumoral administration of OK-MC. There were no significant side effects observed in this treatment. In these patients, approximately 1-10 x 10(7) cells were transferred into the tumor burden. Of the 19 patients, 17 had primary cancer, and in 6 (6/17;35%) of them complete remission (CR) of the tumor was obtained. Partial remission (PR) was attained in 9 of the 17 patients (9/17; 53%), giving the overall response rate of 88%.(ABSTRACT TRUNCATED AT 250 WORDS)
Kubota
E
E
Department of Oral and Maxillofacial Surgery, Saga Medical School, Japan.
Katano
M
M
Kurokawa
H
H
Imamura
H
H
Katsuki
T
T
Yamamoto
H
H
Hisatsugu
T
T
Nagumo
F
F
Tadano
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy; D016207:Cytokines / Q000032:analysis / Q000502:physiology*; D005260:Female; D006131:Growth Inhibitors / Q000032:analysis / Q000502:physiology*; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007124:Immunoenzyme Techniques; D016219:Immunotherapy, Adoptive; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000502:physiology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000502:physiology*; D008222:Lymphokines / Q000032:analysis / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010844:Picibanil / Q000627:therapeutic use*; D012074:Remission Induction; D014407:Tumor Cells, Cultured
D016207:Cytokines; D006131:Growth Inhibitors; D008222:Lymphokines; D010844:Picibanil