Phase I Study of a B Cell-Based and Monocyte-Based Immunotherapeutic Vaccine, BVAC-C in Human Papillomavirus Type 16-or 18-Positive Recurrent Cervical Cancer
Phase I Study of a B Cell-Based and Monocyte-Based Immunotherapeutic Vaccine, BVAC-C in Human Papillomavirus Type 16-or 18-Positive Recurrent Cervical Cancer
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DOI：
10.3390/jcm9010147
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发表时间：
2020-01-01
影响因子：
3.9
通讯作者：
Kim, Byoung-Gie
中科院分区：
文献类型：
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作者：
Choi, Chel Hun;Choi, Hyun Jin;Kim, Byoung-Gie
BVAC-C是一种以人乳头瘤病毒(HPV)16/18 E6/E7基因为载体的重组人乳头瘤病毒(HPV)16/18 E6/E7重组人乳头瘤病毒(HPV)免疫治疗性疫苗。这项I期研究试图确定BVAC-C在铂耐药复发宫颈癌患者中的耐受性和免疫原性。HPV16阳性或18阳性复发性或持续性宫颈癌患者之前至少接受过一次以铂为基础的联合化疗。BVAC-C每4周静脉注射3次，按1×10(7)、4×10(7)或1×10(8)细胞/剂量的3个患者队列设计计划剂量递增。11名患者入选，其中6名(55%)患者在入选前接受了两个或更多的铂类化疗。观察21个周期的治疗相关不良事件(TRAE)。TRAE多为轻度发热(6.55%)或肌痛(4.36%)。未发生剂量限制毒性反应。在可评价的9例患者中，总有效率为11%，有效时间为10个月。5例(56%)患者病情稳定4.2~11个月，总体疗效最佳。中位无进展生存期6.8个月(95%CI，3.2~无穷大个月)，6个月和12个月总生存率分别为89%(95%CI，71~100%)和65%(95%CI，39~100%)。在评估的所有患者中，BVAC-C在接种后诱导了自然杀伤T细胞、自然杀伤细胞和HPV16/18E6/E7特异性T细胞的激活。BVAC-C耐受性良好，在HPV16阳性或18阳性复发宫颈癌患者中表现出持久的抗肿瘤活性和免疫反应。第二阶段疗效试验目前正在进行中。
BVAC-C is a B cell-based and monocyte-based immuno-therapeutic vaccine transfected with a recombinant human papillomavirus (HPV) 16/18 E6/E7 gene and loaded with alpha-galactosyl ceramide, which is a natural killer T cell ligand. This phase I study sought to determine the tolerability and immunogenicity of BVAC-C in platinum-resistant recurrent cervical cancer patients. Patients with HPV 16-positive or 18-positive recurrent or persistent cervical cancer who had received at least one prior platinum-based combination chemotherapy were enrolled. BVAC-C was injected intravenously three times every four weeks, and dose escalation was planned in a three-patient cohort design at doses of 1 x 10(7), 4 x 10(7), or 1 x 10(8) cells/dose. Eleven patients were enrolled, and six (55%) patients had received two or more lines of platinum-based chemotherapy prior to enrollment. Treatment-related adverse events (TRAEs) were observed in 21 cycles. Most TRAEs were mild fever (n = 6.55%) or myalgia (n = 4.36%). No dose-limiting toxicities occurred. The overall response rate was 11% among nine patients evaluable, and the duration of response was 10 months. Five patients (56%) achieved a stable disease for 4.2-11 months as their best overall response. The median progression-free survival in all patients was 6.8 months (95% CI, 3.2 to infinite months), and the overall survival rate at 6 and 12 months was 89% (95% CI, 71 to 100%) and 65% (95% CI, 39 to 100%), respectively. BVAC-C induced the activation of natural killer T cells, natural killer cells, and HPV 16/18 E6/E7-specific T cells upon vaccination in all patients evaluated. BVAC-C was well tolerated and demonstrated a durable anti-tumor activity with an immune response in HPV 16-positive or 18-positive recurrent cervical carcinoma patients. A Phase 2 efficacy trial is currently underway.