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.
Uemura
Hirotsugu
H
Department of Urology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan. huemura@med.kindai.ac.jp
Fujimoto
Kiyohide
K
Mine
Takashi
T
Uejima
Shigeya
S
de Velasco
Marco A
MA
Hirao
Yoshihiko
Y
Komatsu
Nobukazu
N
Yamada
Akira
A
Itoh
Kyogo
K
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