Investigational New Drugs

, Volume 32, Issue 2, pp 235–242

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

Authors

  • Guru Sonpavde
    • Department of Medicine, Section of Medical OncologyBaylor College of Medicine
    • Michael E. DeBakey Veterans Affairs Medical Center
  • Mingjun Wang
    • Center for Inflammation and EpigeneticsThe Methodist Hospital Research Institute and Weill Cornell Medical College of Cornell University
  • Leif E. Peterson
    • Center for BiostatisticsThe Methodist Hospital Research Institute and Weill Cornell Medical College of Cornell University
  • Helen Y. Wang
    • Center for Inflammation and EpigeneticsThe Methodist Hospital Research Institute and Weill Cornell Medical College of Cornell University
  • Teresa Joe
    • Michael E. DeBakey Veterans Affairs Medical Center
  • Martha P. Mims
    • Department of Medicine, Section of Medical OncologyBaylor College of Medicine
  • Dov Kadmon
    • Scott Department of UrologyBaylor College of Medicine
  • Michael M. Ittmann
    • Michael E. DeBakey Veterans Affairs Medical Center
    • Department of PathologyBaylor College of Medicine
  • Thomas M. Wheeler
    • Department of PathologyBaylor College of Medicine
  • Adrian P. Gee
    • Center for Cell and Gene TherapyBaylor College of Medicine
    • Center for Inflammation and EpigeneticsThe Methodist Hospital Research Institute and Weill Cornell Medical College of Cornell University
    • Department of Medicine, Section of Medical OncologyBaylor College of Medicine
    • Michael E. DeBakey Veterans Affairs Medical Center
PHASE I STUDIES

DOI: 10.1007/s10637-013-9960-9

Cite this article as:
Sonpavde, G., Wang, M., Peterson, L.E. et al. Invest New Drugs (2014) 32: 235. doi:10.1007/s10637-013-9960-9

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-1Castration-resistant prostate cancerPeptideImmunotherapyHLA-restrictedCancer vaccines

Copyright information

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