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

Gochi, Akira; Orita, Kunzo; Fuchimoto, Sadanori; Tanaka, Noriaki; Ogawa, Norio

doi:10.1054/bjoc.2000.1599

Cited by 33 publications

(31 citation statements)

References 29 publications

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“…This strategy permits higher and more frequent doses of an anticancer drug for use in tumor therapy. 44 Injection of As 2 O 3 into transplanted esophageal carcinomas resulted in a higher concentration of As 2 O 3 in the tumors than in other organs, and efficiently suppressed tumor growth without systemic side-effects. 10 The strategy adopted in our study is a further advance in that it targets not only primary HCCs, but also targets secondary distant tumors due to the antitumor systemic immunity that develops.…”

Section: Discussionmentioning

confidence: 98%

Arsenic trioxide synergizes with B7H3‐mediated immunotherapy to eradicate hepatocellular carcinomas

Luo

Qiao

Meng

et al. 2005

Intl Journal of Cancer

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Arsenic trioxide (As 2 O 3 ), a valuable anticancer drug for the treatment of acute promyelocytic leukemia, may also have therapeutic potential for the treatment of solid tumors. However, its therapeutic efficacy against solid tumors is lacking even at high dosages. Other therapeutic strategies are required to enhance the efficacy of As 2 O 3 against solid tumors such as hepatocellular carcinoma (HCC), which is refractory to chemotherapy. B7H3, a new member of the B7 family, has been shown to induce antitumor immunity. Intratumoral injection of B7H3 plasmids eradicates small EL-4 lymphomas, but monotherapy is ineffective against large tumors. Here we investigated whether As 2 O 3 would synergize with B7H3 immunotherapy to combat HCC. Large subcutaneous H22 HCCs (0.7-0.8 cm in diameter) established in BALB/c mice were rapidly and completely eradicated when intratumoral administration of As 2 O 3 was preceded by in situ gene transfer of B7H3. In contrast, neither As 2 O 3 nor B7H3 monotherapy was effective. The antitumor activity of As 2 O 3 was attributed to increased tumor-cell apoptosis, perhaps as a result of direct cytotoxicity as well as decreased tumor angiogenesis. Combination therapy generated potent systemic antitumor immunity mediated by CD81 and NK cells that was effective in combating a systemic challenge of 1 3 10 7 parental H22 cells. It led to the simultaneous and complete regression of multiple distant tumor nodules, concomitant with increased levels of serum IFN-c and cytotoxic T lymphocyte (CTL) activity. In conclusion, combining B7H3-mediated immunotherapy with As 2 O 3 warrants investigation as a therapeutic strategy to combat HCC, and other malignancies. ' 2005 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 98%

Arsenic trioxide synergizes with B7H3‐mediated immunotherapy to eradicate hepatocellular carcinomas

Luo

Qiao

Meng

et al. 2005

Intl Journal of Cancer

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“…In a clinical trial with 395 patients (Tanaka et al 1994), a signi® cant improvement in ® ve-year survival was demonstrated for intratumoral OK-432 for patients with stage III disease (48 % survival with intratumoral OK-432 vs 28% for controls). Quite recently, results were presented for a 10-year clinical study of intratumoral immunotherapy with OK-432 in 370 gastric cancer patients (Gochi et al 2001). In the intratumoral study group, patients received endoscopically-injected intratumoral OK-432 one to two weeks before surgery followed by postoperative adjuvant therapy with one intravenous dose of mitomycin plus oral tegafur and intradermal OK-432.…”

Section: Bacterial and Other Immunomodulatorsmentioning

confidence: 99%

Intratumoral cancer chemotherapy and immunotherapy: opportunities for nonsystemic preoperative drug delivery

Goldberg

Hadba

Almond

et al. 2002

Journal of Pharmacy and Pharmacology

178

143

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The recent literature documents the growing interest in local intratumoral chemotherapy as well as systemic preoperative chemotherapy with evidence for improved outcomes using these therapeutic modalities. Nevertheless, with few exceptions, the conventional wisdom and standard of care for clinical and surgical oncology remains surgery followed by radiation and/or systemic chemotherapy, as deemed appropriate based on clinical ndings. This, in spite of the fact that the toxicity of conventional systemic chemotherapy and immunotherapy affords limited effectiveness and frequently compromises the quality of life for patients. Indeed, with systemic chemotherapy, the oncologist (and the patient) often walks a ne line between attempting tumour remission with prolonged survival and damaging the patient's vital functions to the point of death. In this context, it has probably been obvious for more than 100 years, due in part to the pioneering work of Ehrlich (1878), that targeted or localized drug delivery should be a major goal of chemotherapy. However, there is still only limited clinical use of nonsystemic intratumoral chemotherapy for even those high mortality cancers which are characterized by well de ned primary lesions i.e. breast, colorectal, lung, prostate, and skin.There has been a proliferation of intratumoral chemotherapy and immunotherapy research during the past two to three years. It is therefore the objective of this review to focus much more attention upon intratumoral therapeutic concepts which could limit adverse systemic events and which might combine clinically feasible methods for localized preoperative chemotherapy and/or immunotherapy with surgery. Since our review of intratumoral chemo- Given the state-of-the-art in clinical and surgical oncology, and the advances that have been made in intratumoral drug delivery, minimally invasive tumour access i.e. ne needle biopsy, new drugs and drug delivery systems, and preoperative chemotherapy, it is timely to present a review of studies which may suggest future opportunities for safer, more effective, and clinically practical non-systemic therapy. General perspective for traditional systemic therapiesThe toxicity of conventional systemic cancer chemotherapy and immunotherapy has severely limited the safety and eOE ectiveness of such therapy. The quality of life

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“…Adjuvant immunotherapy is expected to exert a synergistic effect with surgical resection. For example: OK-432, a streptococcal preparation, which is one of the most commonly used non-specific enhancer of immune system, demonstrated marginal improvement in survival for patients with stage III gastric cancer [120]. Administration of OK-432 has been reported to induce the release of various cytokines, such as TNF-α, INF-β, IL-8, IL-12, etc., and has also been shown to enhance cytotoxicity against autologous cells.…”

Section: Gastric Cancer Immunotherapymentioning

confidence: 99%

Gastric Cancer Immunotherapy: An Overview

Romano¹,

Uggeri²,

Nespoli³

et al. 2013

JCT

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Gastric adenocarcinoma is the third most common cancer and the second most common cause of death due to cancer worldwide. Surgery is still the major prognostic factor for gastric cancer. Patients who could not be resected have a poor prognosis with survival ranging from 3 to 11 months. There is evidence that surgical operations can cause a variety of immunological disturbances in man both in vivo and in vitro. The postoperative changes in the systemic immune response are proportional to the degree of surgical trauma leading to a generalized state of immunosuppression, which is implicated in the development of septic complications and provided a "fertile soil" for tumor cell metastasis. Immunotherapy may be a potentially promising alternative strategy for gastric cancer. In early clinical trials, systemic immunotherapy included both active vaccination directed against defined tumor-associated antigens expressed in gastric carcinoma cells and passive administration of IL-2 with some evidence of regression of metastatic gastric cancer. Other studies have applied immunotherapy in the adjuvant setting with equally promising results. For example, OK-432, a streptococcal preparation, demonstrated marginal improvement in survival for patients with stage III gastric cancer and a meta-analysis of centrally randomized controlled clinical trials indicated a significant survival benefit with combination OK-432 and chemotherapy compared to chemotherapy alone (p < 0.05). Additional data suggesting a biological and clinical benefit of subcutaneous, preoperative administration of low-dose IL-2 in colon cancer encouraged us to evaluate low-dose IL-2 therapy in the neoadjuvant setting for patients with gastric adenocarcinoma who undergo surgery and to evaluate its effects on systemic and tumor infiltrating lymphocyte numbers. We also sought to determine if neoadjuvant low-dose IL-2 could influence the clinical outcome for patients undergoing gastric resection for cancer. We report the biological, histological and clinical results with the full accrual of patients and a median follow-up of 51 months.

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

Cited by 33 publications

References 29 publications

Arsenic trioxide synergizes with B7H3‐mediated immunotherapy to eradicate hepatocellular carcinomas

Arsenic trioxide synergizes with B7H3‐mediated immunotherapy to eradicate hepatocellular carcinomas

Intratumoral cancer chemotherapy and immunotherapy: opportunities for nonsystemic preoperative drug delivery

Gastric Cancer Immunotherapy: An Overview

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