title: Phase I trial of a B7-1 (CD80) gene modified autologous tumor cell vaccine in combination with systemic interleukin-2 in patients with metastatic renal cell carcinoma.
abstract: OBJECTIVE
  A reason that the immune system may fail to reject tumors is that T cells encounter tumor antigen derived peptides on the surface of tumor cells in a tolerizing rather than activating context since tumor cells do not express T cell co-stimulatory molecules such as B7-1 (CD80). In preclinical models over expression of B7-1 on the surface of tumor cells has been shown to activate T cells which kill tumor cells. We conducted a phase I clinical trial testing this approach in patients with metastatic renal cell carcinoma.
  
  
  METHODS
  Resected tumors from 15 patients were disaggregated and adapted to tissue culture, transduced with the B7-1 gene and injected subcutaneously as a vaccine. The dose of the vaccine was escalated in 3 separate cohorts of patients, and systemic interleukin-2 (IL-2) was administered as an adjuvant designed to enhance the proliferation of the vaccine activated T cells.
  
  
  RESULTS
  Of the 15 patients 9 had measurable disease, 2 had a partial response and 2 had stable disease. Perivascular T cell infiltrates at autologous tumor delayed type hypersensitivity skin test sites developed in 3 of the 4 patients with stable disease or partial response. Although the patients experienced the usual and expected toxicity from the IL-2, there was no significant toxicity observed with the vaccine.
  
  
  CONCLUSIONS
  The B7-1 gene modified autologous tumor cell vaccine is safe and can be combined with systemic IL-2 with acceptable toxicity. Immunological and clinical responses were observed in some of the patients. A phase II trial is reasonable to determine the efficacy of this approach.
authors.affiliation: Interdisciplinary Oncology Program and Genitourinary Program, H. Lee Moffitt Cancer Center, Tampa, Florida 33612, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Antonia
authors.forename: John
authors.initials: J
authors.lastname: Seigne
authors.forename: Jose
authors.initials: J
authors.lastname: Diaz
authors.forename: Carlos
authors.initials: C
authors.lastname: Muro-Cacho
authors.forename: Martine
authors.initials: M
authors.lastname: Extermann
authors.forename: Mary Jane
authors.initials: MJ
authors.lastname: Farmelo
authors.forename: Maria
authors.initials: M
authors.lastname: Friberg
authors.forename: Marwan
authors.initials: M
authors.lastname: Alsarraj
authors.forename: J J
authors.initials: JJ
authors.lastname: Mahany
authors.forename: Julio
authors.initials: J
authors.lastname: Pow-Sang
authors.forename: Alan
authors.initials: A
authors.lastname: Cantor
authors.forename: William
authors.initials: W
authors.lastname: Janssen
mesh_terms: D000328:Adult; D000368:Aged; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007271:Injections, Intradermal; D007376:Interleukin-2 / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010166:Palliative Care; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000276:immunology; D019444:Vaccines, DNA / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D018122:B7-1 Antigen; D019496:Cancer Vaccines; D007376:Interleukin-2; D019444:Vaccines, DNA