The Cytocidal Activity of OK‐432‐activated Mononuclear Cells against Human Glioma Cells is Partly Mediated through the Fas Ligand/Fas System

Toda, Keisuke; Shiraishi, Tetsuya; Hirotsu, Tatsumi; Fukuyama, Kouzou; Mineta, Toshihiro; Kawaguchi, Shojiro

doi:10.1111/j.1349-7006.1996.tb02128.x

Cited by 21 publications

(9 citation statements)

References 24 publications

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“…Recently, it was reported that the expression of perforin in cytotoxic CD8 + T cell is required to moderate allergic airway inflammation [ 29 ]. In line with this, the induction of perforin and enhanced expression of Fas-ligand are shown in OK-432-activated monocytes [ 30 , 31 ], suggesting that an apoptosis-related mechanism might also be involved in controlling pulmonary eosinophilia by OK-432.…”

Section: Discussionmentioning

confidence: 77%

OK-432 Acts as Adjuvant to Modulate T Helper 2 Inflammatory Responses in a Murine Model of Asthma

Tseng

Chan

et al. 2018

Journal of Immunology Research

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Enhanced type 2 helper T (Th2) cell responses to inhaled harmless allergens are strongly associated with the development of allergic diseases. Antigen formulated with an appropriate adjuvant can elicit suitable systemic immunity to protect individuals from disease. Although much has been learned about Th1-favored immunomodulation of OK-432, a streptococcal preparation with antineoplastic activity, little is known about its adjuvant effect for allergic diseases. Herein, we demonstrate that OK-432 acts as an adjuvant to favor a systemic Th1 polarization with an elevation in interferon- (IFN-) γ and ovalbumin- (OVA-) immunoglobulin (Ig) G2a. Prior vaccination with OK-432 formulated against OVA attenuated lung eosinophilic inflammation and Th2 cytokine responses that were caused by challenging with OVA through the airway. This vaccination with OK-432 augmented the ratios of IFN-γ/interleukin- (IL-) 4 cytokine and IgG2a/IgG1 antibody compared to the formulation with Th2 adjuvant aluminum hydroxide (Alum) or antigen only. The results obtained in this study lead us to propose a potential novel adjuvant for clinical use such as prophylactic vaccination for pathogens and immunotherapy in atopic diseases.

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Section: Discussionmentioning

confidence: 77%

OK-432 Acts as Adjuvant to Modulate T Helper 2 Inflammatory Responses in a Murine Model of Asthma

Tseng

Chan

et al. 2018

Journal of Immunology Research

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“…OK-432 is an immunomodulatory agent prepared from an avirulent human strain of Streptococcus pyogenes. It has been shown to induce various cytokines, especially Th1 cytokines (Saito et al, 1982;Yamamoto et al, 1986;Yang et al, 1992) and to upregulate both perforin (Kataoka et al, 1991) and Fas ligand expression (Toda et al, 1996;Sato et al, 1997) of immune cells. In accordance with these findings, OK-432 is also known to enhance or activate the cytotoxic activity of various effector cells (Ishii et al, 1976;Uchida and Micksha, 1983), which may be responsible for its therapeutic effect.…”

Section: Discussionmentioning

confidence: 99%

“…In accordance with these findings, OK-432 is also known to enhance or activate the cytotoxic activity of various effector cells (Ishii et al, 1976;Uchida and Micksha, 1983), which may be responsible for its therapeutic effect. The augmentation of perforin (Kataoka et al, 1991), induction of IL-2 and IFN-γ, and the upregulation of Fas ligand (Toda et al, 1996;Sato et al, 1997) by OK-432 may play a major role in promoting anti-tumour necrotic and apoptotic effects of immune cells like NK cells, LAK cells, CTL (Kagii et al, 1994;Lowin et al, 1994;Lin et al, 1995;Frost et al, 1997), and TILs. These such biological activity of OK-432 are thought to occur at the tumour site in the case of intratumoral injection of OK-432.…”

Section: Discussionmentioning

confidence: 99%

The prognostic advantage of preoperative intratumoral injection of OK-432 for gastric cancer patients

et al. 2001

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SummaryTo investigate, by a multi-institutional randomized trial, the prognostic significance of the augmentation of tumour-infiltrating lymphocytes (TILs) by preoperative intratumoral injection of OK-432 (OK-432 it), a bacterial biological response modifier, in patients with gastric cancer. The 10-year survival and disease-free survival were examined and analysis of the factors showing survival benefit was performed. 370 patients who had undergone curative resection of gastric cancer were enrolled in this study and followed up for 10 years postoperatively. Patients were randomized into either an OK-432 it group or a control group. Ten Klinishe Einheit (KE) of OK-432 was endoscopically injected at 1 to 2 weeks before the operation in the OK-432 it group. Both groups received the same adjuvant chemoimmunotherapy consisting of a bolus injection of mitomycin C (0.4 mg kg Ϫ1 i.v.) and administration of tegafur and OK-432 from postoperative day 14 up to 1 year later. Tegafur (600 mg day Ϫ1) was given orally and OK-432 (5 KE/2 weeks) was injected intradermally for a maintenance therapy. The TILs grades in resected tumour specimens and presence of metastasis and metastatic pattern in dissected lymph nodes were examined. Multivariate analysis was performed to determine the efficacy of OK-432 it on prognostic factors. All patients were followed up for 10 years. The overall 5-and 10-year survival rates and disease-free survival rates of the OK-432 it group were not significantly higher than those of the control group. However, OK-432 it significantly increased the 5-and 10-year survival rates of patients with stage IIIA + IIIB, moderate lymph node metastasis (pN2), and positive TILs. OK-432 it was most effective at prolonging the survival of patients who had both positive TILs and lymph node metastasis. The OK-432 it group with positive TILs showed a significant decrease in metastatic lymph node frequency and in the number of lymph node micrometastatic foci when compared to the control group. This study showed that only one time preoperative OK-432 it, particularly when it triggers TILs, is effective for reduction of regional lymph node metastasis. OK-432 it probably acts partly by eliminating micro-metastatic foci in lymph nodes. Preoperative intratumoral injection of OK-432 is technically very easy and has no serious adverse effects, so it is a promising form of neoadjuvant immunotherapy for advanced gastric cancer.

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“…However, this principle is difficult in practice because the most effective anticancer drugs are generally used during primary treatment. A combination of UFT and OK-432 or another combination of anticancer drugs and an immunopotentiator is recommended in distant metastases because drugs possess not only potent cancer cell growth-inhibitory activity but also induce tumor cell apoptosis [45, 46]and cytotoxic lymphocytes [47, 48]required for successful treatment.…”

Section: Discussionmentioning

confidence: 99%

Clinical Investigation on Pulmonary Metastasis of Head and Neck Carcinomas

et al. 2000

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Objective: To establish a treatment strategy for pulmonary metastases, we clinically investigated the characteristics of distant metastases from head and neck carcinomas. Methods: In 636 head and neck carcinomas, the pathophysiology of distant metastases was investigated by charts, roentgenographies, computed tomographies and scintigraphies. Results: Of the squamous cell carcinomas, oropharyngeal tumors were most highly metastatic, followed by lower gingiva, floor of the mouth, maxillary sinus, and tongue. In distant metastases, 30 (4.7%), 5 (0.8%), and 7 (1.1%) metastasized to the lungs only, lungs and other organs, and organs excluding the lungs, respectively. In pulmonary metastases, the right, left and both lungs were involved in 18, 5, and 8 patients, respectively, although details were not obtained for 4 patients. Pulmonary metastases consisted of 1, 2, and 3 or more tumors in 18, 4, and 6 patients, respectively. Diffuse cancer cell infiltration was observed in 3 patients. Of the 42 patients with distant metastases, 12 patients died of progressive pulmonary metastases, and 5 of these patients manifested only 1 pulmonary lesion throughout life. However, the metastatic pulmonary tumors were controlled surgically or conservatively in 3 patients. Conclusion: These results indicate that distant metastases from head and neck carcinomas involve the lungs most frequently and that chemoimmunotherapy and surgical removal of the metastatic tumors are recommended when indicated.

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The Cytocidal Activity of OK‐432‐activated Mononuclear Cells against Human Glioma Cells is Partly Mediated through the Fas Ligand/Fas System

Cited by 21 publications

References 24 publications

OK-432 Acts as Adjuvant to Modulate T Helper 2 Inflammatory Responses in a Murine Model of Asthma

OK-432 Acts as Adjuvant to Modulate T Helper 2 Inflammatory Responses in a Murine Model of Asthma

The prognostic advantage of preoperative intratumoral injection of OK-432 for gastric cancer patients

Clinical Investigation on Pulmonary Metastasis of Head and Neck Carcinomas

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