title: A randomized pilot trial testing the safety and immunologic effects of a MAGE-A3 protein plus AS15 immunostimulant administered into muscle or into dermal/subcutaneous sites.
abstract: BACKGROUND
  Methods to induce T cell responses to protein vaccines have not been optimized. The immunostimulant AS15 has been administered with the recombinant MAGE-A3 protein (recMAGE-A3) i.m. but not i.d. or s.c. This study tests hypotheses that the i.d./s.c. route is safe and will increase CD4(+) and CD8(+) T cell responses to MAGE-A3.
  
  
  METHODS
  Twenty-five patients with resected stage IIB-IV MAGE-A3(+) melanoma were randomized to immunization with recMAGE-A3 combined with AS15 immunostimulant (MAGE-A3 immunotherapeutic) either i.m. (group A, n = 13) or i.d./s.c. (group B, n = 12). Adverse events were recorded. Ab responses to MAGE-A3 were measured by ELISA. T cell responses to overlapping MAGE-A3 peptides were assessed in PBMC and a sentinel immunized node (SIN) after 1 in vitro stimulation with recMAGE-A3, by IFN-γ ELISPOT assay and by flow cytometry for multifunctional (TNF-α/IFN-γ) responses.
  
  
  RESULTS
  Both routes of immunization were well tolerated without treatment-related grade 3 adverse events. All patients had durable Ab responses. For all 25 patients, the T cell response rate by ELISPOT assay was 30 % in SIN (7/23) but only 4 % (1/25) in PBMC. By flow cytometry, multifunctional CD8(+) T cell responses were identified in one patient in each group; multifunctional CD4(+) T cell response rates for groups A and B, respectively, were 31 and 64 % in SIN and 31 and 50 % in PBMC.
  
  
  CONCLUSIONS
  The MAGE-A3 immunotherapeutic was well tolerated after i.d./s.c. administration, with trends to higher CD4(+) T cell response rates than with i.m. administration. This study supports further study of AS15 by i.d./s.c. administration.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Human Immune Therapy Center, Cancer Center, University of Virginia, 1352 Jordan Hall, P.O. Box 801457, Charlottesville, VA, 22908, USA. cls8h@virginia.edu.
authors.forename: Craig L
authors.initials: CL
authors.lastname: Slingluff
authors.affiliation: Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
authors.forename: Gina R
authors.initials: GR
authors.lastname: Petroni
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Human Immune Therapy Center, Cancer Center, University of Virginia, 1352 Jordan Hall, P.O. Box 801457, Charlottesville, VA, 22908, USA.
authors.forename: Walter C
authors.initials: WC
authors.lastname: Olson
authors.affiliation: Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Smolkin
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Human Immune Therapy Center, Cancer Center, University of Virginia, 1352 Jordan Hall, P.O. Box 801457, Charlottesville, VA, 22908, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Chianese-Bullock
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Human Immune Therapy Center, Cancer Center, University of Virginia, 1352 Jordan Hall, P.O. Box 801457, Charlottesville, VA, 22908, USA.
authors.forename: Ileana S
authors.initials: IS
authors.lastname: Mauldin
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Human Immune Therapy Center, Cancer Center, University of Virginia, 1352 Jordan Hall, P.O. Box 801457, Charlottesville, VA, 22908, USA.
authors.forename: Kelly T
authors.initials: KT
authors.lastname: Smith
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Human Immune Therapy Center, Cancer Center, University of Virginia, 1352 Jordan Hall, P.O. Box 801457, Charlottesville, VA, 22908, USA.
authors.forename: Donna H
authors.initials: DH
authors.lastname: Deacon
authors.affiliation: Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
authors.forename: Nikole E
authors.initials: NE
authors.lastname: Varhegyi
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Human Immune Therapy Center, Cancer Center, University of Virginia, 1352 Jordan Hall, P.O. Box 801457, Charlottesville, VA, 22908, USA.
authors.forename: Sean B
authors.initials: SB
authors.lastname: Donnelly
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Human Immune Therapy Center, Cancer Center, University of Virginia, 1352 Jordan Hall, P.O. Box 801457, Charlottesville, VA, 22908, USA.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Reed
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Human Immune Therapy Center, Cancer Center, University of Virginia, 1352 Jordan Hall, P.O. Box 801457, Charlottesville, VA, 22908, USA.
authors.forename: Kristy
authors.initials: K
authors.lastname: Scott
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Human Immune Therapy Center, Cancer Center, University of Virginia, 1352 Jordan Hall, P.O. Box 801457, Charlottesville, VA, 22908, USA.
authors.forename: Nadejda V
authors.initials: NV
authors.lastname: Galeassi
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Grosh
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D006801:Humans; D007273:Injections, Intramuscular; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology* / Q000627:therapeutic use; D010865:Pilot Projects; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D009363:Neoplasm Proteins
keywords: Cancer vaccines; Human; Melanoma/im; T lymphocytes; TLR agonists; Vaccine adjuvants