Augmentation of antitumor immunity in regional lymph nodes by local immunotherapy

Sakita, Isao; Monden, Takushi; Nagaoka, Hirohito; Katsumoto, Yoshihiro; Wakasugi, Taro; Tomita, Naohiro; Takeda, Tsutomu; Kobayashi, Tetsuro; Shimano, Takashi; Mori, Takesada

doi:10.1007/bf01877423

Cited by 5 publications

(2 citation statements)

References 27 publications

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“…Local immunotherapy with OK-432/fbg induces severe inflammation at the site of injection and in the draining lymph nodes (Sakita et al, 1993). FACS analysis revealed the increased expression of HLA-DR, CD25 and ICAM-1 by TILs about 1 week after the injection of OK-432/fbg.…”

Section: Resultsmentioning

confidence: 96%

Analysis of cytotoxic activity of the CD4+ T lymphocytes generated by local immunotherapy

Katsumoto

Monden²,

Takeda³

et al. 1996

Br J Cancer

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Summary We previously reported that the anti-tumour effect of OK-432 is considerably enhanced by its intratumoral injection together with fibrinogen. In the present study, we generated killer T cells by culturing tumour-infiltrating lymphocytes from thyroid cancer patients who had received this local immunotherapy. Phenotypic analysis revealed that the T cells were positive for CD3+, CD4+, Leu8-, CD45RO+ and T-cell

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Section: Resultsmentioning

confidence: 96%

Analysis of cytotoxic activity of the CD4+ T lymphocytes generated by local immunotherapy

Katsumoto

Monden²,

Takeda³

et al. 1996

Br J Cancer

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“…OK-432 induced a markedly augmented antitumor effect on colorectal cancers when injected intratumorally together with fibrinogen [10]. This type of local immunotherapy is effective not only in inducing local tumor regression but also in activating various cell components of regional lymph nodes [11]. Furthermore, we established cytotoxic CD4+T-cell clone and human monoclonal antibodies derived from such lymph nodes of cancer patients [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

The effect of local immunotherapy for breast cancer using a mixture of OK-432 and fibrinogen supplemented with activated macrophages

et al. 1993

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OK-432 is an immunomodulatory agent prepared from a strain of Streptococcus pyogenes. We have previously reported that intratumoral injection of a mixture of OK-432 and fibrinogen (hereinafter referred to as OK/fbg) is very effective in the local immunotherapy for colorectal cancer. However, we found that the intratumoral injection of OK/fbg into tumor tissues of breast cancers did not always induce a strong antitumor effect. With conventional OK/fbg treatment, tumor necrosis observed in breast cancer tumors was significantly less than that in colorectal cancer tumors; the formation of fibrin meshwork and macrophage infiltration, in particular, were poor. In this study, the OK/fbg mixture was supplemented with activated macrophages for local immunotherapy of breast cancers. Macrophages were prepared from peripheral blood of breast cancer patients and activated with 0.05 mg/ml of OK-432. Between 2-7 days before operation, a single intratumoral injection of the above mixtures was done. The addition of activated macrophages to the OK/fbg mixture resulted in marked degrees of fibrin meshwork formation, macrophage infiltration and cancer cell necrosis. These findings suggest that the recruitment of macrophages in tumor stroma and their activation are necessary for sufficient induction of antitumor immunity, and supplementation of activated macrophages at the site of immune reaction may be an alternative method for reinforcement of the antitumor effect of local immunotherapy.

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Augumentation of splenic antitumor immunity by local immunotherapy in gastric cancer patients

et al. 1997

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We previously reported that the antitumor effect of OK-432, a streptococcal preparation, was markedly augmented when this agent was injected into tumors together with fibrinogen. In order to elucidate the effect of this treatment on the spleen, we assessed splenic function in gastric cancer patients receiving preoperative local immunotherapy with OK-432 and fibrinogen. Immunohistochemical studies of the spleen at 7 days after intratumoral injection therapy revealed numerous macrophages phagocytizing OK-432 in the splenic sinuses. Phenotypic analysis of splenocytes by flow cytometry revealed an increase in the CD4/CD8 ratio and in the expression of HLA-DR, CD25, and Leu M3 by splenic T cells of the patients treated with OK-432 plus fibrinogen when compared to patients treated with OK-432 alone or untreated patients. Splenic T cells from patients treated with OK-432 plus fibrinogen showed significantly higher cytotoxicity against Daudi and K562 cells than T cells from control patients (p < 0.05), and culture of these splenic T cells with recombinant IL-2 induced the expansion of lymphokine-activated killer cells. These results demonstrate that local immunotherapy with a mixture of OK-432 and fibrinogen effectively augumented splenic antitumor immunity in gastric cancer patients.

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Augmentation of antitumor immunity in regional lymph nodes by local immunotherapy

Cited by 5 publications

References 27 publications

Analysis of cytotoxic activity of the CD4+ T lymphocytes generated by local immunotherapy

Analysis of cytotoxic activity of the CD4+ T lymphocytes generated by local immunotherapy

The effect of local immunotherapy for breast cancer using a mixture of OK-432 and fibrinogen supplemented with activated macrophages

Augumentation of splenic antitumor immunity by local immunotherapy in gastric cancer patients

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