Noguchi Masanori, Itoh Kyogo, Suekane Shigetaka, Yao Akihisa, Suetsugu Norie, Katagiri Kazuko, Yamada Akira, Yamana Hideaki, Noda Shinshi
Department of Urology, Kurume University School of Medicine, ururume 830-0011, Japan.
Cancer Sci. 2004 Jan;95(1):77-84. 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.
为了基于循环系统中预先存在的肽特异性细胞毒性T淋巴细胞（CTL）前体，评估肽疫苗接种对转移性激素难治性前列腺癌（HRPC）患者的安全性和毒性，10例人类白细胞抗原（HLA）-A2阳性的转移性HRPC患者被纳入一项I期研究。检测了接种前外周血单核细胞（PBMC）中对16种候选疫苗有反应的肽特异性CTL前体，并仅用阳性肽（最多4种肽）对患者进行疫苗接种随访。定期监测血清前列腺特异性抗原（PSA）水平。肽疫苗接种安全且耐受性良好，无重大不良反应。最常见的毒性是注射部位的皮肤反应。10例患者中有4例观察到对肽的CTL反应增强。10例患者中有7例在接种后血清中也检测到抗肽IgG。1例患者在5次接种后骨盆骨转移消失。3例患者接种后血清PSA水平较基线有所下降，但无患者血清PSA水平下降≥50%。研究患者的中位生存时间为22个月，随访时间为3至27个月。我们认为，细胞免疫和体液免疫反应的增强以及部分患者PSA水平的下降证明对转移性HRPC患者进一步开展肽疫苗接种是合理的。
