Induction of Tumor Growth Inhibitory Factor (TGIF) in Human Mononuclear Cells by OK-432, a Streptococcal Preparation

Overview

Journal Cancer Immunol Immunother

Specialties Allergy & Immunology
Oncology
Pharmacology

Date 1988 Jan 1

PMID 3141056

Citations 3

Authors

M Katano

H Yamamoto

T Mizoguchi

T Hisatsugu

Affiliations

Soon will be listed here.

Abstract

A tumor growth inhibitory factor (TGIF) was induced in the culture supernatant from mixed culture of human peripheral blood mononuclear cells (PBMC) and a streptococcal preparation, OK-432, in vitro. The activity generated in the supernatant increased in a time-dependent fashion and first appeared 6 h after the initiation of culture, reaching its maximum around 48 h. The TGIF was cytostatic against seven of ten human tumor targets, but not against three murine tumor targets. Tumor cell growth was inhibited by a transient contact, i.e., 1 h, with TGIF. The TGIF was produced by lymphocytes but not by monocytes, because the activity was usually enhanced by elimination of plastic-adherent cells from the original PBMC fraction. The TGIF was relatively stable against heating at 56 degrees C for 30 min, but the activity was totally destroyed after heating at 70 degrees C for 5 min. The molecular weight of TGIF was estimated to be about 43 x 10(3) daltons by gel filtration. No interferon (IFN) activity was detected in the TGIF-positive fractions obtained by gel filtration, and the TGIF-positive fractions did not inhibit the growth of tumor necrosis factor (TNF)-sensitive mouse L929 cells. The TGIF activity was not significantly affected in neutralizing tests using specific antibodies against human IFN and TNF. The OK-432 was administered i.p. for management of cancer patients with malignant ascites. Ascites-derived mononuclear cells (ASMC) were obtained before and 3 to 5 days after OK-432 injection. The ASMC obtained after the injection produced TGIF in vitro in the absence of OK-432; the preinjection ASMC showed no such production. A positive correlation was found between TGIF-producing activity by ASMC and the effect of OK-432 injection on ascites volume. These results indicate that TGIF is induced in mononuclear cells by OK-432 not only in vitro but also in vivo and plays an important role in inhibition of tumor growth in cancer patients.

Citing Articles

The cytocidal activity of OK-432-activated mononuclear cells against human glioma cells is partly mediated through the Fas ligand/Fas system.

Toda K, Shiraishi T, Hirotsu T, Fukuyama K, Mineta T, Kawaguchi S Jpn J Cancer Res. 1996; 87(9):972-6.

PMID: 8878461 PMC: 5921210. DOI: 10.1111/j.1349-7006.1996.tb02128.x.

The possible use of spleen cells for the adoptive immunotherapy of cancer patients.

Katano M, Yamamoto H, Kubota E, Nakamura M, Matsuo T, Nagumo F Surg Today. 1993; 23(1):13-20.

PMID: 8461601 DOI: 10.1007/BF00308994.

The antitumor effects of locally injecting human peripheral blood mononuclear cells treated with OK-432 into the tumor site: the possible role of a tumor growth inhibitory factor (TGIF).

Katano M, Mizoguchi T, Yamamoto H, Nakamura M, Matsuo T, Hisatugu T Jpn J Surg. 1990; 20(1):76-82.

PMID: 2304290 DOI: 10.1007/BF02470717.

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