title: Biologic Activity of Autologous, Granulocyte-Macrophage Colony-Stimulating Factor Secreting Alveolar Soft-Part Sarcoma and Clear Cell Sarcoma Vaccines.
abstract: OBJECTIVE
  Alveolar soft-part sarcoma (ASPS) and clear cell sarcoma (CCS) are rare mesenchymal malignancies driven by chromosomal translocations that activate members of the microphthalmia transcription factor (MITF) family. However, in contrast to malignant melanoma, little is known about their immunogenicity. To learn more about the host response to ASPS and CCS, we conducted a phase I clinical trial of vaccination with irradiated, autologous sarcoma cells engineered by adenoviral-mediated gene transfer to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF).
  
  
  METHODS
  Metastatic tumors from ASPS and CCS patients were resected, processed to single-cell suspensions, transduced with a replication-defective adenoviral vector encoding GM-CSF, and irradiated. Immunizations were administered subcutaneously and intradermally weekly three times and then every other week.
  
  
  RESULTS
  Vaccines were successfully manufactured for 11 of the 12 enrolled patients. Eleven subjects received from three to 13 immunizations. Toxicities were restricted to grade 1-2 skin reactions at inoculation sites. Vaccination elicited local dendritic cell infiltrates and stimulated T cell-mediated delayed-type hypersensitivity reactions to irradiated, autologous tumor cells. Antibody responses to tissue-type plasminogen activator (tTPA) and angiopoietins-1/2 were detected. Tumor biopsies showed programmed death-1 (PD-1)-positive CD8(+) T cells in association with PD ligand-1 (PD-L1)-expressing sarcoma cells. No tumor regressions were observed.
  
  
  CONCLUSIONS
  Vaccination with irradiated, GM-CSF-secreting autologous sarcoma cell vaccines is feasible, safe, and biologically active. Concurrent targeting of angiogenic cytokines and antagonism of the PD-1-negative regulatory pathway might intensify immune-mediated tumor destruction.
authors: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Department of Pediatrics, Children's Hospital, Harvard Medical School, Boston, Massachusetts. Department of Pediatrics, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida.
authors: John M
authors: JM
authors: Goldberg
authors: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Department of Pediatrics, Children's Hospital, Harvard Medical School, Boston, Massachusetts. Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors: David E
authors: DE
authors: Fisher
authors: Ludwig Center at Harvard, Harvard Medical School, Boston, Massachusetts. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: George D
authors: GD
authors: Demetri
authors: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts. Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts.
authors: Donna
authors: D
authors: Neuberg
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Cancer Vaccine Center, Center for Immuno-oncology, and Melanoma Disease Center, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Stephen A
authors: SA
authors: Allsop
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Cancer Vaccine Center, Center for Immuno-oncology, and Melanoma Disease Center, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Catia
authors: C
authors: Fonseca
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Cancer Vaccine Center, Center for Immuno-oncology, and Melanoma Disease Center, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Yukoh
authors: Y
authors: Nakazaki
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Cancer Vaccine Center, Center for Immuno-oncology, and Melanoma Disease Center, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: David
authors: D
authors: Nemer
authors: Department of Surgical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Chandrajit P
authors: CP
authors: Raut
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Suzanne
authors: S
authors: George
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Jeffrey A
authors: JA
authors: Morgan
authors: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Department of Pediatrics, Children's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Andrew J
authors: AJ
authors: Wagner
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Cancer Vaccine Center, Center for Immuno-oncology, and Melanoma Disease Center, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Gordon J
authors: GJ
authors: Freeman
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Cancer Vaccine Center, Center for Immuno-oncology, and Melanoma Disease Center, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Jerome
authors: J
authors: Ritz
authors: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Cecilia
authors: C
authors: Lezcano
authors: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Martin
authors: M
authors: Mihm
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Cancer Vaccine Center, Center for Immuno-oncology, and Melanoma Disease Center, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Christine
authors: C
authors: Canning
authors: Ludwig Center at Harvard, Harvard Medical School, Boston, Massachusetts. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Cancer Vaccine Center, Center for Immuno-oncology, and Melanoma Disease Center, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: F Stephen
authors: FS
authors: Hodi
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Cancer Vaccine Center, Center for Immuno-oncology, and Melanoma Disease Center, Dana-Farber Cancer Institute, Boston, Massachusetts. glenn_dranoff@dfci.harvard.edu.
authors: Glenn
authors: G
authors: Dranoff
mesh_terms: D000293:Adolescent; D000328:Adult; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018234:Sarcoma, Alveolar Soft Part / Q000628:therapy*; D018227:Sarcoma, Clear Cell / Q000628:therapy*; D012983:Soft Tissue Neoplasms / Q000628:therapy*; D055815:Young Adult
chemical_list: D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor