title: Clinical response after intradermal immature dendritic cell vaccination in metastatic melanoma is associated with immune response to particulate antigen.
abstract: Metastatic melanoma is poorly responsive to treatment, and immunotherapeutic approaches are potentially beneficial. Predictors of clinical response are needed to identify suitable patients. We sought factors associated with melanoma-specific clinical response following intradermal vaccination with autologous melanoma peptide and particulate hepatitis B antigen (HBsAg)-exposed immature monocyte-derived dendritic cells (MDDC). Nineteen patients with metastatic melanoma received a maximum of 8, 2-weekly vaccinations of DC, exposed to HBsAg in addition to autologous melanoma peptides. A further 3 patients received an otherwise identical vaccine that did not include HBsAg. Patients were assessed 1-2 monthly for safety, disease volume, and cellular responses to HBsAg and melanoma peptide. There was no significant toxicity. Of 19 patients receiving HBsAg-exposed DC, 9 primed or boosted a cellular response to HBsAg, and 10 showed no HBsAg response. HBsAg-specific responses were associated with in vitro T cell responses to melanoma peptides and to phytohemagglutinin (PHA). Zero out of 10 non-HBsAg-responding and 4/9 HBsAg-responding patients achieved objective melanoma-specific clinical responses or disease stabilization - 1 complete and 2 partial responses and 1 case of stable disease ( P=0.018). Development of melanoma-specific cellular immunity and T cell responsiveness to mitogen were greater in the group of patients responding to HBsAg. Therefore stimulation of an immune response to nominal particulate antigen was necessary when presented by melanoma peptide-exposed immature DC, to achieve clinical responses in metastatic melanoma. Since general immune competence may be a determinant of treatment response, it should be assessed in future trials on DC immunotherapy.
authors.affiliation: Department of Surgery, University of Queensland, Queensland. Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Smithers
authors.forename: Kathleen
authors.initials: K
authors.lastname: O'Connell
authors.forename: Susan
authors.initials: S
authors.lastname: MacFadyen
authors.forename: Melita
authors.initials: M
authors.lastname: Chambers
authors.forename: Kathryn
authors.initials: K
authors.lastname: Greenwood
authors.forename: Amanda
authors.initials: A
authors.lastname: Boyce
authors.forename: Ibtissam
authors.initials: I
authors.lastname: Abdul-Jabbar
authors.forename: Kylie
authors.initials: K
authors.lastname: Barker
authors.forename: Karen
authors.initials: K
authors.lastname: Grimmett
authors.forename: Euan
authors.initials: E
authors.lastname: Walpole
authors.forename: Ranjeny
authors.initials: R
authors.lastname: Thomas
mesh_terms: D000276:Adjuvants, Immunologic; D000293:Adolescent; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000494:pharmacology; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000637:transplantation*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006514:Hepatitis B Surface Antigens / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D007117:Immunization, Secondary; D007121:Immunocompetence; D007167:Immunotherapy; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000556:secondary* / Q000601:surgery / Q000628:therapy*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology* / Q000494:pharmacology; D010455:Peptides / Q000276:immunology* / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D012074:Remission Induction; D016896:Treatment Outcome; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D006514:Hepatitis B Surface Antigens; D009363:Neoplasm Proteins; D010455:Peptides; D010835:Phytohemagglutinins; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor