title: Phase 1/2 study of immunotherapy with dendritic cells pulsed with autologous tumor lysate in patients with refractory bone and soft tissue sarcoma.
abstract: 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.
authors.affiliation: Department of Orthopedic Surgery, Kanazawa University School of Medicine, Kanazawa, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Miwa
authors.affiliation: Department of Orthopedic Surgery, Kanazawa University School of Medicine, Kanazawa, Japan.
authors.forename: Hideji
authors.initials: H
authors.lastname: Nishida
authors.affiliation: Department of Orthopedic Surgery, Kanazawa University School of Medicine, Kanazawa, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Tanzawa
authors.affiliation: Department of Orthopedic Surgery, Kanazawa University School of Medicine, Kanazawa, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Takeuchi
authors.affiliation: Department of Orthopedic Surgery, Kanazawa University School of Medicine, Kanazawa, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Department of Orthopedic Surgery, Kanazawa University School of Medicine, Kanazawa, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Department of Disease Control and Homeostasis, Kanazawa University School of Medicine, Kanazawa, Japan.
authors.forename: Eishiro
authors.initials: E
authors.lastname: Mizukoshi
authors.affiliation: Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Nakamoto
authors.affiliation: Department of Disease Control and Homeostasis, Kanazawa University School of Medicine, Kanazawa, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
authors.affiliation: Department of Orthopedic Surgery, Kanazawa University School of Medicine, Kanazawa, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuchiya
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents; D001859:Bone Neoplasms / Q000097:blood / Q000628:therapy*; D002648:Child; D002813:Chondrosarcoma / Q000097:blood / Q000628:therapy; D003713:Dendritic Cells; D018572:Disease-Free Survival; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D051677:Histiocytoma, Malignant Fibrous / Q000097:blood / Q000628:therapy; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D015847:Interleukin-4; D007890:Leiomyosarcoma / Q000097:blood / Q000628:therapy; D007963:Leukocytes, Mononuclear; D008297:Male; D008875:Middle Aged; D012516:Osteosarcoma / Q000097:blood / Q000628:therapy; D010844:Picibanil; D012509:Sarcoma / Q000097:blood / Q000628:therapy*; D018227:Sarcoma, Clear Cell / Q000097:blood / Q000628:therapy; D013584:Sarcoma, Synovial / Q000097:blood / Q000628:therapy; D012983:Soft Tissue Neoplasms / Q000097:blood / Q000628:therapy*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D015847:Interleukin-4; D010844:Picibanil; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: clinical trial; dendritic cells; immunotherapy; sarcoma; tumor lysate