title: A phase I trial of tumor lysate-pulsed dendritic cells in the treatment of advanced cancer.
abstract: OBJECTIVE
  The objectives of this study were to assess the toxicity and immunological response induced by the intradermal (i.d) administration of tumor lysate-pulsed dendritic cells (DCs).
  
  
  METHODS
  Patients with stage IV solid malignancies were treated in cohorts that received 10(6), 10(7), and 10(8) DCs i.d. every 2 weeks for three vaccines. Each vaccine was composed of a mixture of half DCs pulsed with autologous tumor lysate and the other half with keyhole limpet hemocyanin (KLH). Peripheral blood mononuclear cells (PBMCs) harvested 1 month after the last immunization was compared with pretreatment PBMCs for immunological response. Delayed-type hypersensitivity reactivity to tumor antigen and KLH was also assessed.
  
  
  RESULTS
  Fourteen patients received all three vaccines and were evaluable for toxicity and/or immunological monitoring. There were no grade 3 or 4 toxicities associated with the vaccines or major evidence of autoimmunity. Local accumulation of CD4(+) and CD8(+) T cells were found at the vaccination sites. There was a significant proliferative response of PBMCs to KLH induced by the vaccine. In 5 of 6 patients, the vaccine resulted in increased IFN-gamma production by PBMCs to KLH in an ELISPOT assay. Using the same assay, 3 of 7 patients' PBMCs displayed increased IFN-gamma production in response to autologous tumor lysate. One patient with melanoma also was observed to have an increased frequency of MART-1- and gp100-reactive CD8(+) T cells after vaccination. By delayed-type hypersensitivity testing, 8 of 9 and 4 of 10 patients demonstrated reactivity to KLH and autologous tumor, respectively. Two patients with melanoma experienced a partial and a minor response, respectively.
  
  
  CONCLUSIONS
  The administration of tumor lysate-pulsed DCs is nontoxic and capable of inducing immunological response to tumor antigen. Additional studies are necessary to improve tumor rejection responses.
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, Michigan 48109-0932, USA. aechang@umich.edu
authors.forename: Alfred E
authors.initials: AE
authors.lastname: Chang
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Redman
authors.forename: Joel R
authors.initials: JR
authors.lastname: Whitfield
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Nickoloff
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Braun
authors.forename: Peter P
authors.initials: PP
authors.lastname: Lee
authors.forename: James D
authors.initials: JD
authors.lastname: Geiger
authors.forename: James J
authors.initials: JJ
authors.lastname: Mulé
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000032:analysis; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007136:Immunoglobulins / Q000032:analysis; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D007963:Leukocytes, Mononuclear / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D010446:Peptide Fragments / Q000276:immunology; D016896:Treatment Outcome; D014611:Vaccination; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D051940:B7-2 Antigen; D019013:CD40 Antigens; D006684:HLA-DR Antigens; D006433:Hemocyanins; D007136:Immunoglobulins; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D000097802:CD83 Antigen; C497964:CD86 protein, human; C032808:keyhole-limpet hemocyanin