51. Tumoricidal effect of human PBMC following stimulation with OK-432 and its application for locoregional immunotherapy in head and neck cancer patients
- Author
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Jutaroh Tadano, Takeharu Hisatsugu, Fumio Nagumo, Hideo Imamura, T. Katsuki, Eiro Kubota, Hiroshi Yamamoto, Hiroyuki Kurokawa, and Mitsuo Katano
- Subjects
Adult ,Male ,medicine.drug_class ,medicine.medical_treatment ,Monoclonal antibody ,Peripheral blood mononuclear cell ,Immunotherapy, Adoptive ,Immunoenzyme Techniques ,Picibanil ,medicine ,Tumor Cells, Cultured ,Humans ,Interferon gamma ,Killer Cells, Lymphokine-Activated ,Aged ,Aged, 80 and over ,Lymphokines ,business.industry ,Remission Induction ,Immunotherapy ,Middle Aged ,Growth Inhibitors ,Killer Cells, Natural ,Cytokine ,Lymphotoxin ,Otorhinolaryngology ,Cell culture ,Head and Neck Neoplasms ,Immunology ,Carcinoma, Squamous Cell ,Cytokines ,Surgery ,Tumor necrosis factor alpha ,Female ,Oral Surgery ,business ,medicine.drug - Abstract
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)
- Published
- 1993