Investigational New Drugs

, Volume 32, Issue 2, pp 235–242

HLA-restricted NY-ESO-1 peptide immunotherapy for metastatic castration resistant prostate cancer

  • Guru Sonpavde
  • Mingjun Wang
  • Leif E. Peterson
  • Helen Y. Wang
  • Teresa Joe
  • Martha P. Mims
  • Dov Kadmon
  • Michael M. Ittmann
  • Thomas M. Wheeler
  • Adrian P. Gee
  • Rong-Fu Wang
  • Teresa G. Hayes
PHASE I STUDIES

Summary

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). Conclusion 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.

Keywords

NY-ESO-1 Castration-resistant prostate cancer Peptide Immunotherapy HLA-restricted Cancer vaccines 

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Copyright information

© Springer Science+Business Media New York (outside the USA) 2013

Authors and Affiliations

  • Guru Sonpavde
    • 1
    • 2
  • Mingjun Wang
    • 3
  • Leif E. Peterson
    • 4
  • Helen Y. Wang
    • 3
  • Teresa Joe
    • 2
  • Martha P. Mims
    • 1
  • Dov Kadmon
    • 5
  • Michael M. Ittmann
    • 2
    • 6
  • Thomas M. Wheeler
    • 6
  • Adrian P. Gee
    • 7
  • Rong-Fu Wang
    • 3
  • Teresa G. Hayes
    • 1
    • 2
  1. 1.Department of Medicine, Section of Medical OncologyBaylor College of MedicineHoustonUSA
  2. 2.Michael E. DeBakey Veterans Affairs Medical CenterHoustonUSA
  3. 3.Center for Inflammation and EpigeneticsThe Methodist Hospital Research Institute and Weill Cornell Medical College of Cornell UniversityHoustonUSA
  4. 4.Center for BiostatisticsThe Methodist Hospital Research Institute and Weill Cornell Medical College of Cornell UniversityHoustonUSA
  5. 5.Scott Department of UrologyBaylor College of MedicineHoustonUSA
  6. 6.Department of PathologyBaylor College of MedicineHoustonUSA
  7. 7.Center for Cell and Gene TherapyBaylor College of MedicineHoustonUSA

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