Immunotherapy with cancer peptides in combination with intravesical bacillus Calmette–Guerin for patients with non-muscle invasive bladder cancer
Immunotherapy with cancer peptides in combination with intravesical bacillus Calmette–Guerin for patients with non-muscle invasive bladder cancer
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DOI：
10.1007/s00262-018-2197-x
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发表时间：
2018-07
期刊：
影响因子：
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通讯作者：
W. Obara;I. Hara;Y. Kato;Renpei Kato;Keiji Inoue;F. Sato;H. Mimata;Yusuke Nakamura;T. Fujioka-T.-Fujio
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文献类型：
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作者：
W. Obara;I. Hara;Y. Kato;Renpei Kato;Keiji Inoue;F. Sato;H. Mimata;Yusuke Nakamura;T. Fujioka-T.-Fujio
目的利用M期磷蛋白1（MPHOSPH 1）和DEP结构域1（DEPDC 1）两种肽疫苗进行的I期研究显示了治疗晚期膀胱癌的良好效果。因此，我们进一步测试了这些肽的能力，以防止复发后，经尿道切除术的膀胱肿瘤的患者与非肌肉浸润性膀胱癌（NMIBC）。材料和方法127例患者参加了一个多中心，非随机II期临床试验。主要终点是无复发生存率（RFS），次要终点是安全性和免疫应答。除了膀胱内BCG治疗外，还皮下施用HLA-A24限制性肽。探索性终点评估HLA-A*2402阳性（A24（+））和阴性（A24（-））groups.ResultsA 2年RFS率在所有患者之间的差异RFS率为74.0%。A24（+）组（n= 75）和A24（-）组（n= 52）的RFS率分别为76.0%和71.2%。这种疫苗治疗耐受性良好，可行。在A24（+）组中分别观察到75.8%和77.5%的MPHOSPH 1和DEPDC 1肽特异性细胞毒性T淋巴细胞应答。具有两种肽特异性CTL应答的患者比没有CTL应答的患者显示出显著更好的RFS（P= 0.014）。A24（+）组中，注射部位反应阳性（RAI）的患者复发率显著低于RAI阴性的患者（P= 0.0019）。结论癌肽疫苗联合BCG膀胱灌注治疗具有良好的免疫原性和安全性，对预防NMIBC复发有一定的意义。
PurposeA phase I study using two peptide vaccines derived from M phase phosphoprotein 1 (MPHOSPH1) and DEP domain containing 1 (DEPDC1) demonstrated promising results for the treatment of advanced bladder cancer. Therefore, we further tested the ability of these peptides to prevent recurrence after transurethral resection of the bladder tumor in patients with non-muscle invasive bladder cancer (NMIBC).Materials and methods127 patients were enrolled in a multicenter, non-randomized phase II clinical trial. The primary endpoint was recurrence-free survival (RFS) rate, and secondary endpoints were safety and immunological response. HLA-A24-restricted peptides were subcutaneously administered in addition to intravesical BCG therapy. The exploratory endpoint evaluated differences of RFS rate between HLA-A*2402-positive (A24(+)) and -negative (A24(−)) groups.ResultsA 2-year RFS rate in all patients was 74.0%. The RFS rate in the A24(+) group (n= 75) and in the A24(−) group (n= 52) were 76.0 and 71.2%, respectively. This vaccine therapy was well-tolerated and feasible. MPHOSPH1 and DEPDC1 peptide-specific cytotoxic T lymphocyte responses were observed in 75.8 and 77.5% of the A24(+) group, respectively. Patients having both peptide-specific CTL responses showed significantly better RFS than patients without CTL response (P= 0.014). In the A24(+) group, patients who had positive reaction at the injection sites (RAI) had significantly lower rates of recurrence than RAI-negative patients (P= 0.0019).ConclusionsCancer peptide vaccines in combination with intravesical BCG therapy demonstrated good immunogenicity and safety, and may provide benefit for preventing recurrence of NMIBC.