Immunological evaluation of personalized peptide vaccination monotherapy in patients with castration-resistant prostate cancer.
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.
Department of Urology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan. huemura@med.kindai.ac.jp
Hirotsugu
H
Uemura
Kiyohide
K
Fujimoto
Takashi
T
Mine
Shigeya
S
Uejima
Marco A
MA
de Velasco
Yoshihiko
Y
Hirao
Nobukazu
N
Komatsu
Akira
A
Yamada
Kyogo
K
Itoh
D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000627:therapeutic use*; D007987:Gonadotropin-Releasing Hormone / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009919:Orchiectomy; D010455:Peptides / Q000276:immunology*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination
D019496:Cancer Vaccines; D010455:Peptides; D007987:Gonadotropin-Releasing Hormone; D017430:Prostate-Specific Antigen