Phase I trial of patient‐oriented vaccination in HLA‐A2‐positive patients with metastatic hormone‐refractory prostate cancer

• Published in: Cancer science 2004-01, Vol.95 (1), p.77-84
• Main Authors: Noguchi, Masanori, Itoh, Kyogo, Suekane, Shigetaka, Yao, Akihisa, Suetsugu, Norie, Katagiri, Kazuko, Yamada, Akira, Yamana, Hideaki, Noda, Shinshi
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - immunology; Adenocarcinoma - pathology; Adenocarcinoma - therapy; Aged; Antigens; Biological and medical sciences; Cancer Vaccines - adverse effects; Cancer Vaccines - therapeutic use; Cytotoxicity; Drug Resistance, Neoplasm; Gonadotropin-Releasing Hormone - therapeutic use; Histocompatibility antigen HLA; HLA-A2 Antigen - immunology; Humans; Immune response (humoral); Immunization; Immunoglobulin G; Immunoglobulin G - blood; Leukocytes (mononuclear); Lymphocytes T; Male; Medical sciences; Metastases; Metastasis; Middle Aged; Nephrology. Urinary tract diseases; Patients; Pelvis; Peptides; Peripheral blood mononuclear cells; Prostate cancer; Prostate-Specific Antigen - blood; Prostatic Neoplasms - immunology; Prostatic Neoplasms - pathology; Prostatic Neoplasms - therapy; T-Lymphocytes, Cytotoxic - immunology; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Vaccination; Vaccines, Subunit - adverse effects; Vaccines, Subunit - immunology; Vaccines, Subunit - therapeutic use
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/j.1349-7006.2004.tb03174.x

To evaluate the safety and toxicity of peptide vaccination for patients with metastatic hormone‐refractory prostate cancer (HRPC) based on pre‐existing peptide‐specific cytotoxic T‐lymphocyte (CTL) precursors in the circulation, 10 patients positive for human leukocyte antigen (HLA)‐A2 with metastatic HRPC were enrolled in a phase I study. Peptide‐specific CTL‐precursors reactive to 16 kinds of vaccine candidates in the pre‐vaccination peripheral blood mononuclear cells (PBMCs) were measured, and patients were followed by vaccination with only positive peptides (up to 4 kinds of peptides). Serum prostate‐specific antigen (PSA) levels were monitored regularly. The peptide vaccination was safe and well tolerated with no major adverse effects. The most common toxicities were dermatologic reactions at the injection site. Increased CTL response to peptides was observed in 4 of 10 patients. Anti‐peptide IgG was also detected in post‐vaccination sera of 7 of 10 patients. One patient showed the disappearance of a pelvic bone metastasis after five vaccinations. Three patients showed a decrease of serum PSA level from the baseline after the vaccination, but no patients showed a serum PSA level decrease of ∼50%. The median survival duration of study patients was 22 months with follow‐up from 3 to 27 months. We consider that the increase in cellular and humoral immune responses, and decrease in PSA level in some patients justify further development of peptide vaccination for metastatic HRPC patients. (Cancer Sci 2004; 95: 77–84)