title: Immune and clinical responses in patients with metastatic melanoma to CD34(+) progenitor-derived dendritic cell vaccine.
abstract: Immunization to multiple defined tumor antigens for specific immune therapy of human cancer has thus far proven difficult. Eighteen HLA A*0201(+) patients with metastatic melanoma received injections s.c. of CD34(+)progenitor-derived autologous dendritic cells (DCs), which included Langerhans cells. DCs were pulsed with peptides derived from four melanoma antigens [(MelAgs) MelanA/MART-1, tyrosinase, MAGE-3, and gp100], as well as influenza matrix peptide (Flu-MP) and keyhole limpet hemocyanin (KLH) as control antigens. Overall immunological effects were assessed by comparing response profiles using marginal likelihood scores. DC injections were well tolerated except for progressive vitiligo in two patients. DCs induced an immune response to control antigens (KLH, Flu-MP) in 16 of 18 patients. An enhanced immune response to one or more MelAgs was seen in these same 16 patients, including 10 patients who responded to >2 MelAgs. The two patients failing to respond to both control and tumor antigens experienced rapid tumor progression. Of 17 patients with evaluable disease, 6 of 7 patients with immunity to two or less MelAgs had progressive disease 10 weeks after study entry, in contrast to tumor progression in only 1 of 10 patients with immunity to >2 MelAgs. Regression of >1 tumor metastases were observed in seven of these patients. The overall immunity to MelAgs after DC vaccination is associated with clinical outcome (P = 0.015).
authors.affiliation: Baylor Institute for Immunology Research, Dallas, Texas 75204, USA. j.banchereau@baylordallas.edu
authors.forename: J
authors.initials: J
authors.lastname: Banchereau
authors.forename: A K
authors.initials: AK
authors.lastname: Palucka
authors.forename: M
authors.initials: M
authors.lastname: Dhodapkar
authors.forename: S
authors.initials: S
authors.lastname: Burkeholder
authors.forename: N
authors.initials: N
authors.lastname: Taquet
authors.forename: A
authors.initials: A
authors.lastname: Rolland
authors.forename: S
authors.initials: S
authors.lastname: Taquet
authors.forename: S
authors.initials: S
authors.lastname: Coquery
authors.forename: K M
authors.initials: KM
authors.lastname: Wittkowski
authors.forename: N
authors.initials: N
authors.lastname: Bhardwaj
authors.forename: L
authors.initials: L
authors.lastname: Pineiro
authors.forename: R
authors.initials: R
authors.lastname: Steinman
authors.forename: J
authors.initials: J
authors.lastname: Fay
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods; D007801:Langerhans Cells / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D018952:Antigens, CD34; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015789:HLA-A2 Antigen; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin