title: HLA-restricted NY-ESO-1 peptide immunotherapy for metastatic castration resistant prostate cancer.
abstract: BACKGROUND
  Given the immunogenicity of NY-ESO-1 peptides in prostate cancer, a phase I clinical trial was designed to evaluate HLA class-I and class-II restricted NY-ESO-1 peptides in metastatic castration-resistant prostate cancer (mCRPC).
  
  
  METHODS
  Patients with progressive mCRPC, Zubrod Performance Status ≤2, PSA ≥10 ng/ml who had appropriate HLA class I (A2) and class II haplotypes (DR4, DP4) were eligible. Three groups with 3 patients each received the vaccine subcutaneously every 2 weeks for 6 doses. Group 1 received a peptide presented by an HLA class I haplotype (HLA-A2), Group 2 with a peptide presented by HLA class II haplotype (DR4, DP4), and Group 3 with peptides presented by both Class I and II haplotypes. Androgen-deprivation was continued. Owing to a myocardial infarction, the protocol was amended to omit the use of GM-CSF.
  
  
  RESULTS
  Fourteen patients were evaluable for toxicities and 9 received all 6 doses and were evaluable for efficacy. One death from myocardial infarction following GM-CSF occurred in a patient with generalized myalgias. After omitting GM-CSF, no grade >2 toxicities were observed. Among 9 patients evaluable for efficacy, the median PSA doubling time pre-therapy and during therapy were 3.1 and 4.92 months, respectively. NY-ESO-1 specific T-cell response observed by ELISPOT appeared more frequent in docetaxel-naïve patients (4 of 4) than docetaxel-pretreated patients (2 of 5).
  
  
  CONCLUSIONS
  In men with mCRPC, individualized HLA class-I and/or class-II restricted NY-ESO-1 peptides were tolerable, appeared to slow PSA doubling time and yielded antigen-specific T-cell responses more often in chemonaïve patients.
authors.affiliation: Department of Medicine, Section of Medical Oncology, Baylor College of Medicine, Houston, TX, USA; Michael E. DeBakey Veterans Affairs Medical Center, VA 111H, 2002 Holcombe Blvd, Houston, TX 77030, USA.
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
authors.affiliation: Center for Inflammation and Epigenetics, The Methodist Hospital Research Institute and Weill Cornell Medical College of Cornell University, 6670 Bertner Street, Houston, TX 77030, USA.
authors.forename: Mingjun
authors.initials: M
authors.lastname: Wang
authors.affiliation: Center for Biostatistics, The Methodist Hospital Research Institute and Weill Cornell Medical College of Cornell University, Houston, TX, USA.
authors.forename: Leif E
authors.initials: LE
authors.lastname: Peterson
authors.affiliation: Center for Inflammation and Epigenetics, The Methodist Hospital Research Institute and Weill Cornell Medical College of Cornell University, 6670 Bertner Street, Houston, TX 77030, USA.
authors.forename: Helen Y
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Michael E. DeBakey Veterans Affairs Medical Center, VA 111H, 2002 Holcombe Blvd, Houston, TX 77030, USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Joe
authors.affiliation: Department of Medicine, Section of Medical Oncology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Martha P
authors.initials: MP
authors.lastname: Mims
authors.affiliation: Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Dov
authors.initials: D
authors.lastname: Kadmon
authors.affiliation: Michael E. DeBakey Veterans Affairs Medical Center, VA 111H, 2002 Holcombe Blvd, Houston, TX 77030, USA; Department of Pathology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Ittmann
authors.affiliation: Department of Pathology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Wheeler
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Gee
authors.affiliation: Center for Inflammation and Epigenetics, The Methodist Hospital Research Institute and Weill Cornell Medical College of Cornell University, 6670 Bertner Street, Houston, TX 77030, USA.
authors.forename: Rong-Fu
authors.initials: RF
authors.lastname: Wang
authors.affiliation: Department of Medicine, Section of Medical Oncology, Baylor College of Medicine, Houston, TX, USA; Michael E. DeBakey Veterans Affairs Medical Center, VA 111H, 2002 Holcombe Blvd, Houston, TX 77030, USA.
authors.forename: Teresa G
authors.initials: TG
authors.lastname: Hayes
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D008875:Middle Aged; D010455:Peptides / Q000627:therapeutic use*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008565:Membrane Proteins; D010455:Peptides