Tumoricidal effect of human PBMC following stimulation with OK-432 and its application for locoregional immunotherapy in head and neck cancer patients.

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)

• Authors: E Kubota, M Katano, H Kurokawa, H Imamura, T Katsuki, H Yamamoto, T Hisatsugu, F Nagumo, J Tadano
• Journal: Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery (J Craniomaxillofac Surg) Vol. 21 Issue 1 Pg. 30-7 (Jan 1993) ISSN: 1010-5182 [Print] Scotland
• PMID: 8445052 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Growth Inhibitors
• Lymphokines
• Picibanil

Topics

• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Squamous Cell (pathology, therapy)
• Cytokines (analysis, physiology)
• Female
• Growth Inhibitors (analysis, physiology)
• Head and Neck Neoplasms (pathology, therapy)
• Humans
• Immunoenzyme Techniques
• Immunotherapy, Adoptive
• Killer Cells, Lymphokine-Activated (drug effects, physiology)
• Killer Cells, Natural (drug effects, physiology)
• Lymphokines (analysis, physiology)
• Male
• Middle Aged
• Picibanil (therapeutic use)
• Remission Induction
• Tumor Cells, Cultured