title: Synthetic tumor-specific breakpoint peptide vaccine in patients with chronic myeloid leukemia and minimal residual disease: a phase 2 trial.
abstract: BACKGROUND
  Imatinib is the current standard frontline therapy for chronic myelogenous leukemia (CML). In the majority of patients, imatinib induces a complete cytogenetic response (CCyR); however, complete molecular responses are infrequent. The Bcr-Abl fusion creates a unique sequence of amino acids that could constitute a target for immunomodulation.
  
  
  METHODS
  A mixture of heteroclitic and native peptides derived from both b3a2 and b2a2 sequences was used to vaccinate patients with CML in CCyR who were receiving imatinib therapy and who had stable Bcr-Abl transcript levels.
  
  
  RESULTS
  Ten patients were enrolled, all with b2a2 transcripts (including 2 patients who had coexpression of b2a2 and b3a2). Patients had received imatinib for a median of 62 months. Three of 10 patients achieved 1-log reduction in Bcr-Abl transcript levels, including the 2 patients who had received previous interferon therapy, and 3 other patients achieved a major molecular response. The vaccine was tolerated well, and there were no grade > or =3 adverse events. Vaccination did not affect the leukocyte profiles in peripheral blood except for regulatory T cells, which were down-regulated briefly during the late stage of vaccination in patients who achieved approximately 1-log reduction in Bcr-Abl transcript levels.
  
  
  CONCLUSIONS
  The current data suggested that vaccination-related transient disruption of immune tolerance may contribute to the reduction in Bcr-Abl transcripts. Clinically, this Bcr-Abl peptide vaccine may transiently improve the molecular response in a subset of patients with CML.
authors.affiliation: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Nitin
authors.initials: N
authors.lastname: Jain
authors.forename: James M
authors.initials: JM
authors.lastname: Reuben
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Changping
authors.initials: C
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.forename: Bang-Ning
authors.initials: BN
authors.lastname: Lee
authors.forename: Evan N
authors.initials: EN
authors.lastname: Cohen
authors.forename: Theresa
authors.initials: T
authors.lastname: Ebarb
authors.forename: David A
authors.initials: DA
authors.lastname: Scheinberg
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
mesh_terms: D000328:Adult; D001549:Benzamides; D018791:CD4 Lymphocyte Count; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D016130:Immunophenotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010879:Piperazines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000276:immunology; D022223:Vaccines, Subunit / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D014614:Vaccines, Synthetic / Q000627:therapeutic use
chemical_list: D001549:Benzamides; D019496:Cancer Vaccines; D010879:Piperazines; D011743:Pyrimidines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl