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

Guru Sonpavde, Mingjun Wang, Leif E. Peterson, Helen Yicheng Wang, Teresa Joe, Martha P. Mims, Dov Kadmon, Michael M. Ittmann, Thomas M. Wheeler, Adrian P. Gee, Rongfu Wang, Teresa G. Hayes

Research output: Contribution to journalArticle

16 Scopus citations

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). 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.

Original languageEnglish (US)
Pages (from-to)235-242
Number of pages8
JournalInvestigational New Drugs
Volume32
Issue number2
DOIs
StatePublished - Apr 2014

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Oncology

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