picibanil and Soft-Tissue-Neoplasms

There are limited options for the curative treatment of refractory bone and soft tissue sarcomas. The purpose of this phase 1/2 study was to assess the immunological and clinical effects of dendritic cells (DCs) pulsed with autologous tumor lysate (TL) in patients with advanced bone and soft tissue sarcomas.. Thirty-seven patients with metastatic or recurrent sarcomas were enrolled in this study. Peripheral blood mononuclear cells obtained from the patients were suspended in media containing interleukin 4 (IL-4) and granulocyte-macrophage colony-stimulating factor. Subsequently, these cells were treated with TL, tumor necrosis factor α, and OK-432. The DCs were injected into the inguinal or axillary region. One treatment course comprised 6 weekly DC injections. The toxicity, clinical response (tumor volume, serum interferon-γ [IFN-γ], and serum IL-12), and oncological outcomes were observed.. In total, 47 courses of DC therapy were performed in 37 patients. No severe adverse events or deaths associated with the DC injections were observed in the study patients. Increased serum IFN-γ and IL-12 levels were observed 1 month after the DC injection. Among the 37 patients, 35 patients were assessed for clinical responses: 28 patients showed tumor progression, 6 patients had stable disease, and 1 patient showed a partial response 8 weeks after the DC injection. The 3-year overall and progression-free survival rates of the patients were 42.3% and 2.9%, respectively.. Although DC therapy appears safe and resulted in an immunological response in patients with refractory sarcoma, it resulted in an improvement of the clinical outcome in only a small number of patients. Cancer 2017;123:1576-1584. © 2017 American Cancer Society.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Bone Neoplasms; Child; Chondrosarcoma; Dendritic Cells; Disease-Free Survival; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Histiocytoma, Malignant Fibrous; Humans; Immunotherapy; Interferon-gamma; Interleukin-12; Interleukin-4; Leiomyosarcoma; Leukocytes, Mononuclear; Male; Middle Aged; Osteosarcoma; Picibanil; Sarcoma; Sarcoma, Clear Cell; Sarcoma, Synovial; Soft Tissue Neoplasms; Treatment Outcome; Tumor Necrosis Factor-alpha; Young Adult

Dendritic cells (DCs) play a pivotal role in the immune system. There are many reports concerning DC-based immunotherapy. The differentiation and maturation of DCs is a critical part of DC-based immunotherapy. We investigated the differentiation and maturation of DCs in response to various stimuli.. Thirty-one patients with malignant bone and soft tissue tumors were enrolled in this study. All the patients had metastatic tumors and/or recurrent tumors. Peripheral blood mononuclear cells (PBMCs) were suspended in media containing interleukin-4 (IL-4) and granulocyte-macrophage colony stimulating factor (GM-CSF). These cells were then treated with or without 1) tumor lysate (TL), 2) TL + TNF-α, 3) OK-432. The generated DCs were mixed and injected in the inguinal or axillary region. Treatment courses were performed every week and repeated 6 times. A portion of the cells were analyzed by flow cytometry to determine the degree of differentiation and maturation of the DCs. Serum IFN-γ and serum IL-12 were measured in order to determine the immune response following the DC-based immunotherapy.. Approximately 50% of PBMCs differentiated into DCs. Maturation of the lysate-pulsed DCs was slightly increased. Maturation of the TL/TNF-α-pulsed DCs was increased, commensurate with OK-432-pulsed DCs. Serum IFN-γ and serum IL-12 showed significant elevation at one and three months after DC-based immunotherapy.. Although TL-pulsed DCs exhibit tumor specific immunity, TL-pulsed cells showed low levels of maturation. Conversely, the TL/TNF-α-pulsed DCs showed remarkable maturation. The combination of IL-4/GM-CSF/TL/TNF-α resulted in the greatest differentiation and maturation for DC-based immunotherapy for patients with bone and soft tissue tumors.

Topics: Adolescent; Adult; Aged; Bone Neoplasms; Cell Differentiation; Child; Dendritic Cells; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunotherapy; Interleukin-12; Interleukin-4; Male; Middle Aged; Picibanil; Soft Tissue Neoplasms; Tumor Necrosis Factor-alpha

Topics: Antineoplastic Agents; Combined Modality Therapy; Cyanoacrylates; Humans; Infant, Newborn; Lymph; Lymphangioma, Cystic; Picibanil; Postoperative Complications; Radiography; Soft Tissue Neoplasms; Tissue Adhesives

Intralesional injection of OK-432 (lyophilized incubation mixture of group A Streptococcus pyogenes of human origin) is safe and effective therapy for lymphangioma. The authors evaluated the mechanism of this therapy in 6 patients who had cystic lymphangioma. The intracystic fluid of the cystic lymphangioma was aspirated before and after (on days 1 and 4) the OK-432 therapy. Changes in cell populations and cytokine productions in each aspirated fluid were analyzed. White blood cells in the intracystic fluid increased markedly in number. Before OK-432 therapy, 96% of the intracystic white blood cells were lymphocytes, and the remaining were neutrophils and macrophages. On day 1, the percentages of neutrophils and macrophages increased to 72% and 21%, respectively. On day 4, the percentage of lymphocytes increased to 72%. Flow cytometry analysis using monoclonal antibodies showed that the number of natural killer cells (CD56+) and T cells (CD3+) had increased. The activity of cytotoxic tumor necrosis factor (TNF) and interleukin-6 increased immediately after OK-432 injection and remained high in titer until day 4. These findings suggest that the white blood cells induced and activated by OK-432, and the cytokines (including TNF) produced by these cells increased the endothelial permeability, and thus the accelerated lymph drainage and increased lymph flow let to shrinkage of the cystic spaces.

Topics: Adult; Antineoplastic Agents; Child, Preschool; Cytokines; Female; Humans; Infant; Injections, Intralesional; Killer Cells, Natural; Lymphangioma, Cystic; Lymphocyte Activation; Macrophage Activation; Male; Neutrophils; Picibanil; Soft Tissue Neoplasms; Tumor Cells, Cultured

Intratumoral administration of 5 K.E. OK-423 was given every other day for a patient with an abdominal wall recurrence of gastric cancer. After a total dose of 465 K.E. the abdominal tumor turned necrotic and its demarcation was monitored. Finally, the tumor separated and fell from the abdominal wall. Histologically, marked infiltration of neutrophils, lymphocytes, and macrophages were observed in the cancerous tissue. Clinically, local pain lessened and the serum CEA level decreased. PPD and PHA skin tests were markedly stimulated. A long term small-dose intratumoral administration of OK-432 seemed to be effective for a local recurrence of gastric cancer.

Topics: Abdominal Muscles; Adenocarcinoma; Adult; Biological Products; Humans; Male; Picibanil; Soft Tissue Neoplasms; Stomach Neoplasms