1. Phase 1/2 study of immunotherapy with dendritic cells pulsed with autologous tumor lysate in patients with refractory bone and soft tissue sarcoma.
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Miwa, Shinji, Nishida, Hideji, Tanzawa, Yoshikazu, Takeuchi, Akihiko, Hayashi, Katsuhiro, Yamamoto, Norio, Mizukoshi, Eishiro, Nakamoto, Yasunari, Kaneko, Shuichi, and Tsuchiya, Hiroyuki
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CANCER treatment , *SARCOMA , *SOFT tissue tumors , *DENDRITIC cells , *CANCER immunotherapy , *PROGRESSION-free survival , *ANTINEOPLASTIC agents , *BIOLOGICAL products , *BONE tumors , *CLINICAL trials , *COMPARATIVE studies , *GRANULOCYTE-macrophage colony-stimulating factor , *IMMUNOTHERAPY , *INTERFERONS , *INTERLEUKINS , *RESEARCH methodology , *MEDICAL cooperation , *OSTEOSARCOMA , *PROGNOSIS , *RESEARCH , *TUMOR necrosis factors , *EVALUATION research , *TREATMENT effectiveness , *CHONDROSARCOMA , *LEIOMYOSARCOMA , *MONONUCLEAR leukocytes , *TUMOR treatment , *THERAPEUTICS ,CONNECTIVE tissue tumors - Abstract
Background: 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.Methods: 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.Results: 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.Conclusions: 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. [ABSTRACT FROM AUTHOR]- Published
- 2017
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