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

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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.

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Acknowledgments

This work was in part supported by grants from the National Institutes of Health (Grant number NIH Specialized Programs of Research Excellence CA58204) as well as by grants from National Cancer Institute, NIH (R01CA090327, R01CA101795, R01CA116408 and R01CA121191) to R.F.W. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Ethical standards

The research complies with the current laws of the United States.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Medicine, Section of Medical Oncology, Baylor College of Medicine, Houston, TX, USA

    Guru Sonpavde, Martha P. Mims & Teresa G. Hayes

  2. Michael E. DeBakey Veterans Affairs Medical Center, VA 111H, 2002 Holcombe Blvd, Houston, TX, 77030, USA

    Guru Sonpavde, Teresa Joe, Michael M. Ittmann & Teresa G. Hayes

  3. 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

    Mingjun Wang, Helen Y. Wang & Rong-Fu Wang

  4. Center for Biostatistics, The Methodist Hospital Research Institute and Weill Cornell Medical College of Cornell University, Houston, TX, USA

    Leif E. Peterson

  5. Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA

    Dov Kadmon

  6. Department of Pathology, Baylor College of Medicine, Houston, TX, USA

    Michael M. Ittmann & Thomas M. Wheeler

  7. Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA

    Adrian P. Gee

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  1. Guru Sonpavde
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  2. Mingjun Wang
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  9. Thomas M. Wheeler
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  11. Rong-Fu Wang
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  12. Teresa G. Hayes
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Corresponding authors

Correspondence to Rong-Fu Wang or Teresa G. Hayes.

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Guru Sonpavde and Mingjun Wang receive equal credit.

Rong-Fu Wang and Teresa G. Hayes share the corresponding authorship.

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Sonpavde, G., Wang, M., Peterson, L.E. et al. HLA-restricted NY-ESO-1 peptide immunotherapy for metastatic castration resistant prostate cancer. Invest New Drugs 32, 235–242 (2014). https://doi.org/10.1007/s10637-013-9960-9

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  • DOI: https://doi.org/10.1007/s10637-013-9960-9

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