title: A phase I trial of SD-9427 (progenipoietin) with a multipeptide vaccine for resected metastatic melanoma.
abstract: OBJECTIVE
  The melanoma tumor antigen epitope peptides MART-1(26-35 (27L)), gp100(209-217 (210M)),and tyrosinase(368-376 (370D)) were emulsified with incomplete Freund's adjuvant and administered with SD-9427 (progenipoietin), an agonist of granulocyte colony-stimulating factor and the FLT-3 receptor, to evaluate the toxicities of and immune responses to this regimen as primary end points and time to relapse and survival as secondary end points.
  
  
  METHODS
  Fifteen patients with high-risk resected stage III and IV melanoma were enrolled. Each patient received peptides + incomplete Freund's adjuvant with SD-9427 at doses of either 10, 20, or 40 microg/kg s.c. for 3 days before and 7 days after each vaccination. Immunizations were administered every month for 6 months and then administered once 6 months later. A leukapheresis to obtain peripheral blood mononuclear cells for immune analyses as well as skin testing with peptides and recall antigens was performed before and after vaccination. IFN- gamma release assay, ELISPOT, and MHC-peptide tetramer analysis were performed using peripheral blood mononuclear cells collected before and after vaccination to evaluate peptide-specific cytotoxic T-cell responses.
  
  
  RESULTS
  Local pain and granuloma formation and fatigue of grade I or II were the most common side effects. One patient developed antibody-mediated leukopenia and transient grade III neutropenia that resolved after stopping SD-9427. Six of 12 patients tested developed a positive skin test response to one or more of the peptides. Seven of 10 patients tested demonstrated an immune response to at least one peptide when evaluated by IFN-gamma release assay and ELISPOT assay after vaccination, as did 11 of 12 patients analyzed by MHC-peptide tetramer assay. Four of 15 patients have relapsed with a median follow-up of 20 months, and 1 patient in this high-risk group has died of disease.
  
  
  CONCLUSIONS
  SD-9427 with a multipeptide vaccine was generally well tolerated, although one patient developed reversible antibody-mediated neutropenia. These data suggest that the majority of patients with resected melanoma mount an antigen-specific immune response against a multipeptide vaccine administered with SD-9427.
authors.affiliation: Department of Medicine, Divisions of Hematology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
authors.forename: Vinod
authors.initials: V
authors.lastname: Pullarkat
authors.forename: Peter P
authors.initials: PP
authors.lastname: Lee
authors.forename: Ronaldo
authors.initials: R
authors.lastname: Scotland
authors.forename: Valerie
authors.initials: V
authors.lastname: Rubio
authors.forename: Susan
authors.initials: S
authors.lastname: Groshen
authors.forename: Conway
authors.initials: C
authors.lastname: Gee
authors.forename: Roy
authors.initials: R
authors.lastname: Lau
authors.forename: Jolie
authors.initials: J
authors.lastname: Snively
authors.forename: Shirley
authors.initials: S
authors.lastname: Sian
authors.forename: Susan L
authors.initials: SL
authors.lastname: Woulfe
authors.forename: Richard A
authors.initials: RA
authors.lastname: Wolfe
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Weber
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines / Q000378:metabolism*; D003115:Colony-Stimulating Factors / Q000494:pharmacology* / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D000939:Epitopes; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007937:Leukapheresis; D058965:MART-1 Antigen; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000096:biosynthesis; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010455:Peptides / Q000737:chemistry; D011994:Recombinant Proteins; D013997:Time Factors; D016896:Treatment Outcome; D014612:Vaccines / Q000378:metabolism; D022223:Vaccines, Subunit / Q000378:metabolism; D058951:gp100 Melanoma Antigen
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D003115:Colony-Stimulating Factors; D016207:Cytokines; D000939:Epitopes; D058965:MART-1 Antigen; C548667:MLANA protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D010455:Peptides; D011994:Recombinant Proteins; D014612:Vaccines; D022223:Vaccines, Subunit; D058951:gp100 Melanoma Antigen; C434603:progenipoietin-1; D014442:Monophenol Monooxygenase