title: Induction of immune responses and clinical efficacy in a phase II trial of IDM-2101, a 10-epitope cytotoxic T-lymphocyte vaccine, in metastatic non-small-cell lung cancer.
abstract: OBJECTIVE
  Generation of broad cytotoxic T-lymphocyte responses against multiple epitopes and tumor-associated antigens (TAAs) may provide effective immunotherapy in patients with cancer. We evaluated a single-vial peptide vaccine consisting of nine HLA-A2 supertype-binding epitopes (two native and seven analog epitopes modified for optimal HLA binding or T-cell receptor stimulation) covering five TAAs and the universal helper pan-DR epitope, formulated as a stable emulsion with incomplete Freund's adjuvant (Montanide ISA 51; Seppic SA, Paris, France). The clinical efficacy, safety, and multiepitope immunogenicity of IDM-2101 was evaluated in patients with stage IIIB or IV non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  A total of 63 patients were enrolled who were positive for HLA-A2. End points included survival, safety, and immune response. IDM-2101 (previously EP-2101) was administered every 3 weeks for the first 15 weeks, then every 2 months through year 1, then quarterly through year 2, for a total of 13 doses. Epitope-specific cytotoxic and helper T-lymphocyte immunogenic responses were measured by the interferon gamma enzyme-linked immunosorbent spot assay.
  
  
  RESULTS
  No significant adverse events were noted. Low-grade erythema and pain at the injection site were the most common adverse effects. One-year survival in the treated patients was 60%, and median survival was 17.3 months. One complete and one partial response were identified. Survival was longer in patients demonstrating an immune response to epitope peptides (P < .001).
  
  
  CONCLUSIONS
  IDM-2101 was well tolerated, and evidence of efficacy was suggested.
authors.affiliation: Mary Crowley Cancer Research Centers, Dallas, TX, USA.
authors.forename: Minal
authors.initials: M
authors.lastname: Barve
authors.forename: James
authors.initials: J
authors.lastname: Bender
authors.forename: Neil
authors.initials: N
authors.lastname: Senzer
authors.forename: Casey
authors.initials: C
authors.lastname: Cunningham
authors.forename: F Anthony
authors.initials: FA
authors.lastname: Greco
authors.forename: David
authors.initials: D
authors.lastname: McCune
authors.forename: Ronald
authors.initials: R
authors.lastname: Steis
authors.forename: Hung
authors.initials: H
authors.lastname: Khong
authors.forename: Donald
authors.initials: D
authors.lastname: Richards
authors.forename: Joe
authors.initials: J
authors.lastname: Stephenson
authors.forename: Prasanthi
authors.initials: P
authors.lastname: Ganesa
authors.forename: Jackie
authors.initials: J
authors.lastname: Nemunaitis
authors.forename: Glenn
authors.initials: G
authors.lastname: Ishioka
authors.forename: Beena
authors.initials: B
authors.lastname: Pappen
authors.forename: Michael
authors.initials: M
authors.lastname: Nemunaitis
authors.forename: Michael
authors.initials: M
authors.lastname: Morse
authors.forename: Bonnie
authors.initials: B
authors.lastname: Mills
authors.forename: Phillip B
authors.initials: PB
authors.lastname: Maples
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Sherman
authors.forename: John J
authors.initials: JJ
authors.lastname: Nemunaitis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000517:prevention & control* / Q000556:secondary*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology* / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; C532151:IDM 2101