Immunological evaluation of personalized peptide vaccination monotherapy in patients with castration-resistant prostate cancer.

Abstract

We previously reported that personalized peptide vaccine (PPV) therapy in combination with leutenizing hormone-releasing hormone (LH-RH) analog and estramustine phosphate in certain cases is safe and capable of inducing both immune responses and clinical responses for metastatic castration-resistant prostate cancer (CRPC) patients. In the present study, PPV monotherapy was given to CRPC patients. Twenty-three patients with metastatic CRPC were treated with PPV without any additional treatment modalities, including LH-RH analogs. Samples were analyzed for peptide-specific cytotoxic T-lymphocyte (CTL) precursor analysis and peptide-reactive IgG. Toxicity and immunological and clinical responses were assessed on a three-monthly basis. Seventeen patients were available for immunological and clinical evaluation. The vaccines were well tolerated, with grade 3 erythema at injection sites in only one patient. Augmentation of CTL or IgG responses to at least one of the peptides was observed in six of 17 (35%) and 15 of 17 (88%) patients tested, respectively. Among 57 peptides used, 9 and 36 peptides induced CTL and IgG responses, respectively. Delayed-type hypersensitivity reaction was observed in eight of 17 patients. More than 30% prostate-specific antigen (PSA) decline was observed in four of 17 patients. Of these, one patient achieved a complete PSA response and another patient showed a partial PSA response with profound shrinking of lymph node metastases and prostate. The overall median survival time was 24 months (range, 5-37 months). These results suggest that PPV monotherapy appears to be safe and capable of inducing peptide-specific immune responses and clinical responses in CRPC patients. This trial was registered with University Hospital Medical Information Network (UMIN) number R000003339.

• Authors: Hirotsugu Uemura, Kiyohide Fujimoto, Takashi Mine, Shigeya Uejima, Marco A de Velasco, Yoshihiko Hirao, Nobukazu Komatsu, Akira Yamada, Kyogo Itoh
• Journal: Cancer science (Cancer Sci) Vol. 101 Issue 3 Pg. 601-8 (Mar 2010) ISSN: 1349-7006 [Electronic] England
• PMID: 20128819 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cancer Vaccines
• Peptides
• Gonadotropin-Releasing Hormone
• Prostate-Specific Antigen

Topics

• Aged
• Aged, 80 and over
• Cancer Vaccines (therapeutic use)
• Gonadotropin-Releasing Hormone (therapeutic use)
• Humans
• Male
• Middle Aged
• Orchiectomy
• Peptides (immunology)
• Prostate-Specific Antigen (blood)
• Prostatic Neoplasms (immunology, mortality, therapy)
• T-Lymphocytes, Cytotoxic (immunology)
• Vaccination