title: A safety and feasibility study of an allogeneic colon cancer cell vaccine administered with a granulocyte-macrophage colony stimulating factor-producing bystander cell line in patients with metastatic colorectal cancer.
abstract: BACKGROUND
  Despite recent advances in earlier detection and improvements in chemotherapy, the 5-year survival rate of patients with metastatic colorectal carcinoma remains poor. Immunotherapy is a potentially effective therapeutic approach to the treatment of colorectal carcinoma. Preclinical studies have supported the antitumor activity of immunization with a granulocyte-macrophage colony-stimulating factor (GM-CSF) producing murine colon tumor cell vaccine.
  
  
  METHODS
  A novel colorectal cancer vaccine composed of irradiated, allogeneic human colon cancer cells and GM-CSF-producing bystander cells was developed and tested in combination with a single intravenous low dose of cyclophosphamide in a phase 1 study of patients with metastatic colorectal cancer.
  
  
  RESULTS
  A total of nine patients were enrolled onto and treated in this study. Six patients had a history of colorectal adenocarcinoma hepatic metastases and underwent curative metastasectomy, while three other patients had unresectable stage IV disease. This study demonstrates the safety and feasibility of this vaccine administered in patients with metastatic colorectal cancer. At last follow-up, the six patients who underwent curative metastasectomy survived longer than 36 months, and four of these six patients were without disease recurrence. Immunologic correlate results suggest that the GM-CSF-producing colon cancer vaccine enhances the production of anti-MUC1 antibodies.
  
  
  CONCLUSIONS
  This vaccine is feasible and safe. Future investigation of the efficacy and antitumor immunity of this vaccine is warranted.
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.forename: Barish H
authors.initials: BH
authors.lastname: Edil
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Soares
authors.forename: Khaled
authors.initials: K
authors.lastname: El-Shami
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Uram
authors.forename: Carol
authors.initials: C
authors.lastname: Judkins
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.forename: Beth
authors.initials: B
authors.lastname: Onners
authors.forename: Daniel
authors.initials: D
authors.lastname: Laheru
authors.forename: Drew
authors.initials: D
authors.lastname: Pardoll
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Jaffee
authors.forename: Richard D
authors.initials: RD
authors.lastname: Schulick
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D019496:Cancer Vaccines / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D015179:Colorectal Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007167:Immunotherapy; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008207:Lymphatic Metastasis; D016173:Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging; D011379:Prognosis; D012449:Safety; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D018906:Antineoplastic Agents, Alkylating; D019496:Cancer Vaccines; D016173:Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide