Vaccine Research Group, Research Department, Center of Genetic Engineering and Biotechnology, Camagüey, Cuba.
Department of Urology, Oncological Hospital Camagüey, Camagüey, Cuba.
Technol Cancer Res Treat. 2023 Jan-Dec;22:15330338231207318. doi: 10.1177/15330338231207318.
A gonadotropin-releasing hormone (GnRH)-based therapeutic vaccine candidate against hormone-sensitive prostate cancer has demonstrated its safety and signs of efficacy in phase I/II trials. In this study, we characterized the isotype/subclass profiles of the anti-GnRH humoral response generated by the vaccination and analyzed its association with patients' clinical outcomes.
The immunoglobulin isotypes and IgG subclasses of the antibody responses of 34 patients included in a randomized, open, prospective phase I/II clinical trial were characterized. Every patient included in the study had a diagnosis of locally advanced prostate adenocarcinoma at stages 3 and 4 and received immunization with the vaccine candidate. Additionally, serum testosterone and prostate specific antigen (PSA) concentrations, serving as indicators of tumor response, were determined. The type of anti-GnRH antibody response was correlated to the time elapsed until the first biochemical recurrence in patients and the outcome of the disease.
All patients developed strong and prolonged anti-GnRH antibody responses, resulting in a short- to mid-term decrease in serum testosterone and PSA levels. Following immunizations, anti-GnRH antibodies of the IgM/IgG and IgG1/IgG3 subclasses were observed. Following radiotherapy, the humoral response switched to IgG (IgG1/IgG4). Patients who experienced a short-term biochemical relapse were characterized by significantly higher levels of anti-GnRH IgG titers, particularly IgG1 and IgG4 subclasses. These characteristics, along with a high response of specific IgM antibodies at the end of immunizations and the development of anti-GnRH IgA antibody responses following radiotherapy, were observed in patients whose disease progressed, compared to those with controlled disease.
The nature of the humoral response against anti-GnRH, induced by vaccination may play a key role in activating additional immunological mechanisms. Collectively, these mechanisms could contribute significantly to the regulation of tumor growth.
促性腺激素释放激素（GnRH）为基础的治疗性疫苗候选物对激素敏感的前列腺癌已在 I/II 期临床试验中证明了其安全性和疗效迹象。在这项研究中，我们描述了接种疫苗产生的抗 GnRH 体液反应的同种型/亚类谱，并分析了其与患者临床结果的关系。
对 34 名纳入随机、开放、前瞻性 I/II 期临床试验的患者的抗体反应免疫球蛋白同种型和 IgG 亚类进行了特征描述。研究中的每位患者均被诊断为局部晚期前列腺腺癌，分期为 3 期和 4 期，并接受候选疫苗免疫接种。此外，还测定了血清睾酮和前列腺特异性抗原（PSA）浓度，作为肿瘤反应的指标。抗 GnRH 抗体反应的类型与患者发生首次生化复发的时间以及疾病的结局相关。
所有患者均产生了强烈且持久的抗 GnRH 抗体反应，导致血清睾酮和 PSA 水平在短期至中期下降。免疫接种后观察到 IgM/IgG 和 IgG1/IgG3 亚类的抗 GnRH 抗体。放疗后，体液反应转为 IgG（IgG1/IgG4）。发生短期生化复发的患者的抗 GnRH IgG 滴度显著较高，特别是 IgG1 和 IgG4 亚类。与疾病得到控制的患者相比，疾病进展的患者在免疫接种结束时具有较高的特异性 IgM 抗体反应和放疗后抗 GnRH IgA 抗体反应的特征。
疫苗接种诱导的抗 GnRH 体液反应的性质可能在激活额外的免疫机制中发挥关键作用。这些机制共同可能对肿瘤生长的调节起到重要作用。
