Department of Urology, Iwate medical University School of Medicine, Morioka, Japan.
Department of Urology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Ann Oncol. 2017 Apr 1;28(4):798-803. doi: 10.1093/annonc/mdw675.
S-288310, a cancer peptide vaccine composed of two HLA-A*24:02-restricted peptides derived from two oncoantigens, DEP domain-containing 1 (DEPDC1) and M-phase phosphoprotein 1 (MPHOSPH1), was investigated in urothelial carcinoma (UC) of the bladder.
Thirty eight HLA-A*24:02-positive patients with progressive UC were enrolled in this study. In the phase I part of the study, three patients each were treated with S-288310 at 1 mg or 2 mg/peptide subcutaneously once a week to evaluate safety and tolerability. In the phase II, 32 patients were randomized to receive either 1 mg or 2 mg to evaluate the difference in cytotoxic T lymphocytes (CTL) induction and safety.
S-288310 was safe and well tolerated in the phase I. Of 27 patients evaluable for immune responses in the phase II, there was no difference in CTL induction rate between the 1 mg (100%) and 2 mg (80.0%) groups. Of 32 patients receiving S-288310 in the phase II, the most frequent drug-related AE was the injection site reaction that was observed in 29 patients (90.6%), but none of the patients discontinued administration due to these reactions and no dose relationship in the frequency and severity was observed. The objective response rate of the 32 patients was 6.3% and the disease control rate was 56.3%. The median overall survival (OS) rates for patients vaccinated with S-288310 after one regimen of chemotherapy, 2 regimens, or 3 or more were 14.4, 9.1 and 3.7 months, respectively, and 32.2% of patients post first-line treatment were alive at 2 years. OS of patients who showed CTL induction to both peptides was longer than that of those with CTL induction to no or one peptide.
S-288310 was well-tolerated and effectively induced peptide-specific CTLs, which were correlated with longer survival for patients with UC of the bladder.
JapicCTI-090980.
S-288310 是一种癌症肽疫苗，由两个 HLA-A*24:02 限制性肽组成，来源于两个肿瘤抗原，DEP 结构域包含 1（DEPDC1）和 M 期磷酸蛋白 1（MPHOSPH1），用于研究膀胱癌中的尿路上皮癌。
38 名 HLA-A*24:02 阳性的进展性 UC 患者入组本研究。在研究的 I 期部分，三名患者分别接受 S-288310 1mg 或 2mg/肽皮下注射，每周一次，以评估安全性和耐受性。在 II 期，32 名患者随机接受 1mg 或 2mg 以评估细胞毒性 T 淋巴细胞（CTL）诱导和安全性的差异。
S-288310 在 I 期的安全性和耐受性良好。在 II 期可评估免疫反应的 27 名患者中，1mg（100%）和 2mg（80.0%）组的 CTL 诱导率无差异。在 32 名接受 S-288310 的 II 期患者中，最常见的药物相关不良反应是注射部位反应，29 名患者（90.6%）观察到该反应，但无患者因这些反应而停止治疗，且频率和严重程度无剂量关系。32 名患者的客观缓解率为 6.3%，疾病控制率为 56.3%。接受 S-288310 化疗 1 个疗程、2 个疗程或 3 个疗程以上的患者中位总生存期（OS）分别为 14.4、9.1 和 3.7 个月，一线治疗后 32.2%的患者在 2 年内存活。同时诱导两种肽的 CTL 诱导的患者的 OS 长于无或一种肽诱导的患者。
S-288310 耐受性良好，可有效诱导肽特异性 CTL，与膀胱癌患者的生存时间延长相关。
JapicCTI-090980。
