title: Lack of T-cell responses following autologous tumour lysate pulsed dendritic cell vaccination, in patients with relapsed osteosarcoma.
abstract: BACKGROUND
  Immunotherapy using autologous dendritic cell (DC) vaccination has not been systematically evaluated in osteosarcoma. We therefore conducted a phase I trial to assess feasibility, safety and tumour-specific immune responses in patients with relapsed disease.
  
  
  METHODS
  Of 13 recruited patients with relapsed osteosarcoma, 12 received 3 weekly vaccines of autologous DCs matured with autologous tumour lysate and keyhole limpet haemocyanin (KLH), to a maximum of 6 vaccinations. An additional 3 paediatric patients afflicted with other tumour types and with relapsed disease received vaccines generated with identical methodology. Immune responses were assessed using an ELISpot assay for the detection of interferon gamma, whilst interleukin-2 and granzyme B were additionally assessed in cases where interferon-γ responses were induced.
  
  
  RESULTS
  In total 61 vaccines, of homogeneous maturation phenotype and viability, were administered with no significant toxicity. Only in 2 out of 12 treated osteosarcoma cases was there an induction of specific T-cell immune response to the tumour, whilst a strong but non-specific immune response was induced in 1 further osteosarcoma patient. Immune response against KLH was induced in only 3 out of 12 osteosarcoma patients. In contrast, three additional non-osteosarcoma patients showed significant T-cell responses to vaccine.
  
  
  CONCLUSIONS
  We have shown the strategy of DC vaccination in relapsed osteosarcoma is safe and feasible. However, significant anti-tumour responses were induced in only 2 out of 12 vaccinated patients with no evidence of clinical benefit. Comparison of results with identically treated control patients suggests that osteosarcoma patients might be relatively insensitive to DC-based vaccine treatments.
authors.affiliation: Unit of Molecular Haematology and Cancer Biology, University College London Institute of Child Health, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Himoudi
authors.forename: R
authors.initials: R
authors.lastname: Wallace
authors.forename: K L
authors.initials: KL
authors.lastname: Parsley
authors.forename: K
authors.initials: K
authors.lastname: Gilmour
authors.forename: A-U
authors.initials: AU
authors.lastname: Barrie
authors.forename: K
authors.initials: K
authors.lastname: Howe
authors.forename: R
authors.initials: R
authors.lastname: Dong
authors.forename: N J
authors.initials: NJ
authors.lastname: Sebire
authors.forename: A
authors.initials: A
authors.lastname: Michalski
authors.forename: A J
authors.initials: AJ
authors.lastname: Thrasher
authors.forename: J
authors.initials: J
authors.lastname: Anderson
mesh_terms: D000293:Adolescent; D000328:Adult; D019496:Cancer Vaccines; D003713:Dendritic Cells / Q000166:cytology; D005240:Feasibility Studies; D005260:Female; D053804:Granzymes / Q000096:biosynthesis; D006433:Hemocyanins / Q000737:chemistry; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008297:Male; D012516:Osteosarcoma / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D010641:Phenotype; D012008:Recurrence; D013601:T-Lymphocytes / Q000166:cytology*; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; D007376:Interleukin-2; D007371:Interferon-gamma; D006433:Hemocyanins; D053804:Granzymes; C032808:keyhole-limpet hemocyanin