■B细胞淋巴瘤-超大(Bcl-XL)蛋白在癌细胞抵抗凋亡中起重要作用。临床前研究表明,用Bcl-XL衍生肽接种可以诱导肿瘤特异性T细胞反应,从而消除癌细胞。此外,新型佐剂CAF®09b的临床前研究表明,腹膜内(IP)注射该佐剂可以改善免疫系统的激活。在这项研究中,激素敏感性前列腺癌(PC)患者接受了由Bcl-XL肽组成的疫苗,CAF®09b作为佐剂.主要目的是评估IP和肌内(IM)给药的耐受性和安全性,确定最佳给药途径,并表征疫苗的免疫原性。
■纳入20例患者。总共安排了6次疫苗接种:A组(IM到IP注射),十名患者每两周接受三次疫苗IM;经过三周的停顿,患者随后每两周接受3种疫苗IP接种.在组B(IP到IM注入)中,10名患者首先接种了IP疫苗,随后在类似的疫苗接种时间表下进行IM。根据不良事件通用术语标准(CTCAEv.4.0),通过记录和评估不良事件(AE)来评估安全性。通过酶联免疫斑点和流式细胞术分析疫苗诱导的免疫应答。
■未报告严重的不良事件。尽管在所有患者中发现针对Bcl-XL肽的T细胞应答增加,与A组患者相比,B组中更多的患者对疫苗表现出更早和更强的免疫反应。我们证明了疫苗诱导的针对Bcl-XL肽中嵌入的患者特异性CD4和CD8T细胞表位的免疫,以及疫苗接种后CD4和CD8T细胞活化标志物CD107a和CD137的增加.中位随访21个月,没有患者出现有临床意义的疾病进展.
■Bcl-XL-肽-CAF®09b疫苗在l激素敏感型PC患者中是可行且安全的。此外,该疫苗具有免疫原性,能够引发CD4和CD8T细胞应答,初次IP给药可在更多og患者中引发早期和高水平的疫苗特异性应答.
■https://clinicaltrials.gov,标识符NCT03412786。
The B-cell lymphoma-extra-large (Bcl-XL) protein plays an important role in cancer cells\' resistance to apoptosis. Pre-clinical studies have shown that vaccination with Bcl-XL-derived peptides can induce tumor-specific T cell responses that may lead to the elimination of cancer cells. Furthermore, pre-clinical studies of the novel adjuvant CAF®09b have shown that intraperitoneal (IP) injections of this adjuvant can improve the activation of the immune system. In this
study, patients with hormone-sensitive prostate cancer (PC) received a vaccine consisting of Bcl-XL-peptide with CAF®09b as an adjuvant. The primary aim was to evaluate the tolerability and safety of IP and intramuscular (IM) administration, determine the optimal route of administration, and characterize vaccine immunogenicity.
Twenty patients were included. A total of six vaccinations were scheduled: in Group A (IM to IP injections), ten patients received three vaccines IM biweekly; after a three-week pause, patients then received three vaccines IP biweekly. In Group B (IP to IM injections), ten patients received IP vaccines first, followed by IM under a similar vaccination schedule. Safety was assessed by logging and evaluating adverse events (AE) according to Common Terminology Criteria for Adverse Events (CTCAE v. 4.0). Vaccines-induced immune responses were analyzed by Enzyme-Linked Immunospot and flow cytometry.
No serious AEs were reported. Although an increase in T cell response against the Bcl-XL-peptide was found in all patients, a larger proportion of patients in group B demonstrated earlier and stronger immune responses to the vaccine compared to patients in group A. Further, we demonstrated vaccine-induced immunity towards patient-specific CD4, and CD8 T cell epitopes embedded in Bcl-XL-peptide and an increase in CD4 and CD8 T cell activation markers CD107a and CD137 following vaccination. At a median follow-up of 21 months, no patients had experienced clinically significant disease progression.
The Bcl-XL-peptide-CAF®09b vaccination was feasible and safe in patients with l hormone-sensitive PC. In addition, the vaccine was immunogenic and able to elicit CD4 and CD8 T cell responses with initial IP administration eliciting early and high levels of vaccine-specific responses in a higher number og patients.
https://clinicaltrials.gov, identifier NCT03412786.