B细胞淋巴瘤-extra-large（Bcl-XL）蛋白在癌细胞抵抗凋亡方面起着重要作用。临床前研究表明，Bcl-XL衍生的肽疫苗接种可以引起肿瘤特异性T细胞反应，可能导致癌细胞消除。此外，新型佐剂CAF®09b的临床前研究表明，该佐剂的腹腔内注射可以提高免疫系统的激活程度。本研究对荷尔蒙敏感的前列腺癌（PC）患者接种了Bcl-XL肽和CAF®09b佐剂组成的疫苗。主要目的是评估腹腔内和肌肉注射的耐受性和安全性，确定最佳的注射途径，以及表征疫苗的免疫原性。共有20名患者参加了本研究。计划总共接种六次疫苗：在A组（肌肉注射到腹腔内注射）中，十名患者每两周肌肉注射三次疫苗；三周休息后，患者再进行腹腔内注射三次。在B组（腹腔内注射到肌肉注射），十名患者首先进行腹腔内注射疫苗，随后根据类似的疫苗接种计划进行肌肉注射。根据不良事件通用术语标准（CTCAE v.4.0）记录和评估了安全性。通过酶联免疫斑点法和流式细胞术分析了感染后的免疫反应。没有报告严重的不良反应。虽然所有的患者都出现了对Bcl-XL肽的T细胞反应增加，但在B组中，更高比例的患者表现出了更早更强的疫苗特异性反应。此外，我们证明了疫苗引起的对患者特异性CD4和CD8T细胞表位的免疫反应，这些表位嵌入在Bcl-XL肽中，并且在疫苗接种后CD4和CD8T细胞激活标记物CD107a和CD137也有所增加。在中位随访21个月后，没有患者经历了临床意义的疾病进展。Bcl-XL肽-CAF®09b疫苗在荷尔蒙敏感的PC患者中是可行且安全的。此外，在更多的患者中，初次腹腔内注射可以引起早期高水平的疫苗特异性反应。编号NCT03412786，版权所有©2023 Mørk、Kongsted、Westergaard、Albieri、Granhøj、Donia、Martinenaite、Holmström、Madsen、Kverneland、Kjeldsen、Holmstroem、Lorentzen、Nørgaard、Andreasen、Wood、Christensen、Klausen、Hadrup、thor Straten、Andersen和Svane。

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.Copyright © 2023 Mørk, Kongsted, Westergaard, Albieri, Granhøj, Donia, Martinenaite, Holmström, Madsen, Kverneland, Kjeldsen, Holmstroem, Lorentzen, Nørgaard, Andreasen, Wood, Christensen, Klausen, Hadrup, thor Straten, Andersen and Svane.