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Phase 1/2 study of immunotherapy with dendritic cells pulsed with autologous tumor lysate in patients with refractory bone and soft tissue sarcoma
Author(s) -
Miwa Shinji,
Nishida Hideji,
Tanzawa Yoshikazu,
Takeuchi Akihiko,
Hayashi Katsuhiro,
Yamamoto Norio,
Mizukoshi Eishiro,
Nakamoto Yasunari,
Kaneko Shuichi,
Tsuchiya Hiroyuki
Publication year - 2017
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.30606
Subject(s) - medicine , soft tissue , refractory (planetary science) , immunotherapy , sarcoma , soft tissue sarcoma , peripheral blood mononuclear cell , tumor necrosis factor alpha , gastroenterology , pathology , cancer , biochemistry , physics , chemistry , astrobiology , in vitro
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 .