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Cureus Apr 2024We present a case of lung adenocarcinoma with malignant pleural effusion. Nineteen days after pleurodesis using minocycline and OK-432 (picibanil), pembrolizumab...
We present a case of lung adenocarcinoma with malignant pleural effusion. Nineteen days after pleurodesis using minocycline and OK-432 (picibanil), pembrolizumab monotherapy was initiated. Four days later, the patient experienced a persistent cough. Chest computed tomography showed that ground-glass opacity appeared on the same side as pleurodesis and spread bilaterally thereafter, which was diagnostic of immune checkpoint inhibitors (ICI)-related pneumonitis. As he presented a severe respiratory failure, corticosteroid therapy was administered. Two weeks later, respiratory failure completely resolved and the abnormal shadows dramatically improved. Our results indicate that severe ICI-related pneumonitis can develop within a short period after pleurodesis.
PubMed: 38784310
DOI: 10.7759/cureus.58798 -
Journal of Immunology Research 2018Enhanced type 2 helper T (Th2) cell responses to inhaled harmless allergens are strongly associated with the development of allergic diseases. Antigen formulated with an...
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-) 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-/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.
Topics: Adjuvants, Immunologic; Alum Compounds; Animals; Asthma; Cell Differentiation; Disease Models, Animal; Humans; Immunoglobulin G; Immunomodulation; Immunotherapy; Interferon-gamma; Male; Mice; Mice, Inbred C57BL; Picibanil; Th1 Cells; Th2 Cells
PubMed: 30402504
DOI: 10.1155/2018/1697276 -
Annals of Thoracic and Cardiovascular... Jan 2024A prolonged air leak (PAL) is one of the common postoperative complications of pulmonary resection. The aim of this study was to evaluate the efficacy and safety of...
PURPOSE
A prolonged air leak (PAL) is one of the common postoperative complications of pulmonary resection. The aim of this study was to evaluate the efficacy and safety of pleurodesis with sterile talc or OK-432 for postoperative air leak.
METHODS
Patients with postoperative air leak who received chemical pleurodesis using sterile talc or OK-432 were retrospectively identified from medical records data. For pleurodesis with either agent, prior assessment and approval by the hospital safety department were carried out for each case, in addition to individual consent.
RESULTS
Between February 2016 and June 2022, 39 patients had PALs and underwent chemical pleurodesis. Among them, 24 patients received pleurodesis with talc (Talc group) and 15 with OK-432 (OK-432 group). The leak resolved after less than two pleurodesis treatments in 22 patients (91.7%) in the Talc group compared with 14 patients (93.3%) in the OK-432 group. Pleurodesis significantly increased white blood cell counts, C-reactive protein concentration, and body temperature in the OK-432 group compared with that in the Talc group (p <0.001, p = 0.003, and p <0.001, respectively).
CONCLUSIONS
Pleurodesis with talc may be an effective treatment option for postoperative air leak. Our findings suggest that talc was as effective as OK-432 and resulted in a milder systemic inflammatory response.
Topics: Humans; Talc; Pleurodesis; Picibanil; Retrospective Studies; Treatment Outcome
PubMed: 37648484
DOI: 10.5761/atcs.oa.23-00115 -
Cancer Immunology, Immunotherapy : CII Sep 2003For vaccinations based on dendritic cells (DCs), maturation of DCs is critical to the induction of T-cell responses. We tested the efficacy of streptococcal preparation...
For vaccinations based on dendritic cells (DCs), maturation of DCs is critical to the induction of T-cell responses. We tested the efficacy of streptococcal preparation OK-432 as a Good Manufacturing Practice (GMP)-grade maturation agent. OK-432 is currently used in Japan as a cancer immunotherapy drug. Immature monocyte-derived dendritic cells (imMo-DCs) isolated from human peripheral blood monocytes stimulated with granulocyte-macrophage colony stimulating factor and interleukin-4 were exposed to maturation factors, i.e., lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha) plus prostaglandin E2 (PGE2), and OK-432 for 2 days. OK-432 increased expression of activation- and maturation-related molecules such as HLA-DR, CD80, CD83, and CD86 in imMo-DCs at levels similar to that of TNF-alpha plus PGE2, and higher than that of LPS. All agents examined induced allogeneic T-cell proliferation at a similar level. Only OK-432 caused significant production of interleukin-12 (IL-12) p70 and interferon gamma (IFN-gamma) at both the mRNA and protein levels in imMo-DCs. Neutralizing antibody against IL-12 p70 blocked IFN-gamma secretion from OK-432-stimulated Mo-DCs. IL-12 p70 produced by OK-432-stimulated imMo-DCs induced secretion of IFN-gamma by CD4+ T cells. OK-432 and LPS activated nuclear factor kappa B (NF-kappaB) in imMo-DCs. Both secretion of IL-12 p70 and IFN-gamma and activation of NF-kappaB induced by OK-432 were suppressed when imMo-DCs were pretreated with cytochalasin B. These results indicate that uptake of OK-432 by imMo-DCs is an early critical event for IL-12 p70 production and that NF-kappaB activation induced by OK-432 also contributes partially to IL-12 p70 production. In conclusion, OK-432 is a GMP-grade maturation agent and may be a potential tool for DC-based vaccine therapies.
Topics: Cells, Cultured; Cytochalasin B; Dendritic Cells; Enzyme Activation; Humans; Interferon-gamma; Interleukin-12; Lymphocyte Activation; Monocytes; Picibanil; Protein Serine-Threonine Kinases; T-Lymphocytes; NF-kappaB-Inducing Kinase
PubMed: 14627128
DOI: 10.1007/s00262-003-0394-7 -
British Journal of Cancer Nov 2003In total, 16 patients with cytologically proven malignant effusion from colorectal cancer were treated by locoregional administration of the streptococcal preparation... (Clinical Trial)
Clinical Trial
Locoregional immunotherapy of malignant effusion from colorectal cancer using the streptococcal preparation OK-432 plus interleukin-2: induction of autologous tumor-reactive CD4+ Th1 killer lymphocytes.
In total, 16 patients with cytologically proven malignant effusion from colorectal cancer were treated by locoregional administration of the streptococcal preparation OK-432 alone or OK-432 plus the T-cell growth factor interleukin (IL)-2, and the action mechanism of the treatment was studied. A positive clinical response, showing a cytologic disappearance of cancer cells and decrease of effusion, was observed in nine of 11 (82%) patients treated with OK-432 alone and in all five patients treated with OK-432 plus IL-2. Flow cytometric analysis revealed that OK-432 plus IL-2 locally induced acute inflammation-like responses, including serial cellular infiltrations of granulocyte migration within a matter of hours, and activation of macrophages and T lymphocyte involvement within the following days, and that a predominant expansion of CD3+CD4+ lymphocytes (CD: cluster of differentiation) was induced by in vitro stimulation with IL-2 of locoregional cells after the OK-432 administration (OK/IL-2AK cells). The OK/IL-2AK cells produced tumour necrosis factor-alpha and interferon-gamma, but these cells did not produce IL-4 and IL-6. The OK/IL-2AK cells expressed potent killing activity against autologous tumour cells. This activity was abrogated by treatment of the lymphocytes with anti-CD3, -CD4, -TCRalphabeta antibody, and by the treatment of target cells with anti-human leukocyte antigen (HLA)-DR antibody. The OK/IL-2AK cells expressed Fas-L gene, and flow cytometric analysis demonstrated HLA-DR expression in approximately 75% of CEA+ or cytokeratin+ effusion cells. TCRVbeta gene analysis of the OK/IL-2AK cells showed an oligoclonal usage of TCRbeta20, which was also involved in the cytotoxic mechanism of the OK/IL-2AK cells. Single-strand conformational polymorphism analysis demonstrated the clonotypes for the TCRVbeta20 gene, and the CDR3s of the gene were sequenced. The clonotypic PCR using the TCRVbeta20-CDR3 sequences could detect the CDR3-identical TCRs in effusion lymphocytes from the other patients. Taken together, it is suggested that locoregional administration of OK-432 plus IL-2 is highly effective for the management of malignant effusion from colorectal cancer. OK-432 plus IL-2 induces autologous tumour-reactive CD4+ Th1 killer lymphocytes, which recognise tumour antigen(s) presented with HLA class II molecules on effusion tumour cells by means of preferential usage of TCRVbeta20. The clonotypic PCR using the TCRVbeta20-CDR3 sequences may be informative for treating malignant effusion from colorectal cancer using OK-432 plus IL-2.
Topics: Adult; Aged; Ascites; CD4-Positive T-Lymphocytes; Colorectal Neoplasms; Female; Humans; Immunotherapy; Interleukin-2; Lymphocyte Activation; Male; Middle Aged; Paracentesis; Picibanil; Pleural Effusion; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 14612896
DOI: 10.1038/sj.bjc.6601379 -
The Biochemical Journal Mar 2001Phosphorylation/dephosphorylation processes are known to control the activity of several transcription factors. The nutrition-dependent expression of sucrase-isomaltase...
Phosphorylation/dephosphorylation processes are known to control the activity of several transcription factors. The nutrition-dependent expression of sucrase-isomaltase and Na+/glucose co-transporter 1, two proteins implicated in the intestinal absorption of glucose, has been shown to be closely related to modifications of hepatocyte nuclear factor 1 (HNF1) activity. This study was conducted to determine whether phosphorylation/dephosphorylation processes could control HNF1 activity. We show that expression of the gene encoding sucrase-isomaltase is inhibited in the enterocytic Caco-2 clone TC7 by okadaic acid at a concentration that is known to inhibit protein phosphatases 1/2A and that does not affect cell viability. At the same concentration, phosphorylation of the HNF1alpha and HNF1beta isoforms is greatly enhanced and their DNA-binding capacity is decreased. The phosphorylation state of HNF1beta isoforms directly affects their DNA-binding capacity. In contrast, the decreased DNA-binding activity of the HNF1alpha isoforms, which was observed after the inhibition of protein phosphatases 1/2A, is due to a net decrease in their total cellular and nuclear amounts. Such an effect results from a decrease in both the HNF1alpha mRNA levels and the half-life of the protein. This is the first evidence for the implication of protein phosphatases 1/2A in the control of the activity of HNF1 isoforms. Moreover, these results emphasize a physiological role for the balance between phosphatases and kinases in the nutrition-dependent regulation of HNF1-controlled genes.
Topics: Caco-2 Cells; DNA; DNA-Binding Proteins; Electrophoresis, Polyacrylamide Gel; Enzyme Inhibitors; Glucose; Hepatocyte Nuclear Factor 1; Hepatocyte Nuclear Factor 1-alpha; Hepatocyte Nuclear Factor 1-beta; Humans; Liver Glycogen; Nuclear Proteins; Phosphoprotein Phosphatases; Picibanil; Protein Conformation; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factors
PubMed: 11171107
DOI: 10.1042/0264-6021:3540301 -
The Keio Journal of Medicine Mar 1990Synergistic effect of recombinant IFN-gamma (IFN-gamma) and OK-432, a streptococcal preparation, using chromium release assay was studied in vitro on killer cell...
Synergistic effect of recombinant IFN-gamma (IFN-gamma) and OK-432, a streptococcal preparation, using chromium release assay was studied in vitro on killer cell induction. The target cells utilized for assay were a human leukemia cell line K562, a human renal carcinoma cell line KU-2, autologous normal kidney tissues and autologous renal cell carcinomas. Culture supernatant of peripheral blood lymphocytes (PBL) and OK-432 (designated as OK conditioned medium or OK-CM) demonstrated enhanced cytotoxicity of fresh PBL against these target cells. Killer cell activity against autologous cancer cells could be also induced from PBL of renal cell carcinoma patients. Pretreatment of PBL with IFN-gamma revealed synergistic effect of OK-CM on killer cell induction. OK-CM derived from patients was shown to contain IL-2 activity as well as high titer of interferon. Neutralizing monoclonal antibody against IFN-gamma and IL-2 receptor demonstrated reduction of cytotoxicity. These results suggested potential benefit of sequential use of IFN-gamma and OK-432 for the treatment of metastatic renal cell carcinoma.
Topics: Biological Products; Carcinoma, Renal Cell; Cytotoxicity, Immunologic; Humans; Immunotherapy; Interferon-gamma; Kidney Neoplasms; Picibanil; Tumor Cells, Cultured
PubMed: 2113148
DOI: 10.2302/kjm.39.21 -
Cancer Immunology, Immunotherapy : CII Feb 1996The antitumor effects of immunotherapy using streptococcal preparations (OK-432), recombinant granulocyte-colony-stimulating factor (rG-CSF) and recombinant... (Comparative Study)
Comparative Study
The antitumor effects of immunotherapy using streptococcal preparations (OK-432), recombinant granulocyte-colony-stimulating factor (rG-CSF) and recombinant interleukin-2 (rIL-2) were examined for human hepatocellular carcinoma (HCC). Following subcutaneous injection of OK-432 (2 KE) and rG-CSF (50-60 microg), low-dose intratumoral administration of OK-432 (3-12 KE) was performed. Thereafter, 2 x 10(5) JRU of rIL-2 was subcutaneously injected. This therapeutic regimen was repeated twice. Serum alpha-fetoprotein levels were markedly decreased in three of seven patients with HCC by this treatment. Post-therapeutic histological examination revealed that trabecular cords or pseudoglandular arrangements of tumor cells were completely disordered in all cases and that extensive infiltration of lymphocytes into the tumor stroma was present in five cases. The number of CD4- and CD57-positive cells among tumor-infiltrating lymphocytes after immunotherapy was significantly higher than that in patients without immunotherapy (P <0.01). These findings suggest that even a small intratumoral injection of OK-432 can induce extensive infiltration of helper/inducer and natural killer cells into the tumor stroma when combined with subcutaneous injection of OK-432, rG-CSF and rIL-2 and that these cells might play important roles in tumor cytotoxicity.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Drug Administration Schedule; Female; Granulocyte Colony-Stimulating Factor; Humans; Immunohistochemistry; Immunotherapy; Interleukin-2; Leukocyte Count; Liver Neoplasms; Male; Middle Aged; Neutrophils; Picibanil; Recombinant Proteins; alpha-Fetoproteins
PubMed: 8620522
DOI: 10.1007/s002620050262 -
Nihon Hinyokika Gakkai Zasshi. the... Mar 1991Immunotherapy gained popularity as a treatment modality for malignant diseases in the 1960s. A number of trials, using tumor vaccines, immunopotentiators, interferons,... (Review)
Review
Immunotherapy gained popularity as a treatment modality for malignant diseases in the 1960s. A number of trials, using tumor vaccines, immunopotentiators, interferons, cytokines and others, demonstrated antitumor effects in several urological malignancies, and, to date, immunotherapy plays a major role in treatment of advanced renal cell carcinoma and superficial bladder carcinoma. Interferon or interleukin-2, which became available for large scale clinical trial with the development of bioengineering, however, were shown to be not effective as initially expected, by single agent. Rational design of new strategies with multiple agents in combination based on basic and clinical research, should provide progress in treatment of urological malignancies.
Topics: BCG Vaccine; Immunotherapy; Immunotherapy, Adoptive; Interferons; Interleukin-2; Killer Cells, Lymphokine-Activated; Picibanil; RNA; Urologic Neoplasms
PubMed: 1712869
DOI: 10.5980/jpnjurol1989.82.361 -
British Journal of Cancer Jan 1996We 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... (Comparative Study)
Comparative Study
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 receptor (TCR)alpha beta+, as well as showing strong surface expression of HLA-DR, CD25, LFA-1 and ICAM-1. The generated CD4+ T cells secreted interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, TNF-beta, and interleukin (IL)-6 (but not IL-4), and exhibited a high level of cytolytic activity against several tumour cell lines. The cytolytic activity of these T cells for Daudi cells was inhibited by preincubation with an anti-intercellular adhesion molecule (ICAM)-1 antibody, but not by preincubation with anti-TCR alpha beta, anti-CD2, or anti-LFA-1 antibodies. Pretreatment with anti-ICAM-1 antibody inhibited T-cell cytolytic activity, but not conjugation with target cells. In addition, incubation with immobilised anti-ICAM-1 enhanced the secretion of IFN-gamma by T cells. We conclude that ICAM-1 expressed on the effector cytotoxic CD4+ T lymphocytes delivers regulatory signals that enhance IFN-gamma secretion.
Topics: Adjuvants, Immunologic; Antineoplastic Agents; CD4-Positive T-Lymphocytes; Cell Adhesion; Cytotoxicity, Immunologic; Humans; Immunotherapy; Intercellular Adhesion Molecule-1; Killer Cells, Natural; Lymphocytes, Tumor-Infiltrating; Neoplasms; Picibanil; T-Lymphocytes, Cytotoxic; Thyroid Neoplasms; Tumor Cells, Cultured
PubMed: 8554971
DOI: 10.1038/bjc.1996.20