A Phase II Trial to Evaluate the Safety and Immunogenicity of Two Doses of a Folate Receptor Alpha Vaccine in Patients with Triple-Negative Breast Cancer.

We previously reported a phase I trial evaluating a folate receptor alpha (FRα) vaccine administered with cyclophosphamide (CP), demonstrating excellent safety and immunogenicity.

我们之前报告了一项I期试验，评估了与环磷酰胺（CP）联合使用的叶酸受体α（FRα）疫苗，显示出极佳的安全性和免疫原性。

To simplify the vaccine strategy for ease of use, we report here the results of a randomized phase II trial evaluating a lower vaccine dose alongside the original dose, administered with or without CP pretreatment.

为了简化疫苗接种策略以便于使用，我们报告了一项随机II期试验的结果，该试验评估了与原始剂量一起使用较低剂量的疫苗，无论是否使用CP预处理。

patients_and_methods

Patients with triple-negative breast cancer who completed all systemic and local therapies were assigned to receive either low-dose (825 μg) or high-dose (2.5 mg) vaccine peptides plus GM-CSF in six 4-week cycles, with or without CP prior to vaccination.

完成所有系统性和局部治疗的三阴性乳腺癌患者被分配接受低剂量（825微克）或高剂量（2.5毫克）疫苗肽加上GM-CSF的六次4周周期治疗，无论是否在接种疫苗前使用CP。

Safety was monitored, and immunogenicity was evaluated before and after vaccination.

监测了安全性，并在接种疫苗前后评估了免疫原性。

Results

A total of 80 patients were dosed with vaccine, and 58 patients were evaluable for immunogenicity.

共有80名患者接受了疫苗接种，其中58名患者可评估免疫原性。

Vaccination was well tolerated and elicited immunity in 83% of patients.

疫苗接种耐受性良好，并在83%的患者中引发了免疫反应。

Levels of FRα-specific T cells were high, persistent, and comparable with T-cell levels against tetanus toxoid.

针对FRα特异性T细胞的水平很高，持续性强，并且与针对破伤风类毒素的T细胞水平相当。

No differences in immunity were observed between the two doses.

两种剂量之间未观察到免疫差异。

CP pretreatment also did not affect the immune responses.

CP预处理也未影响免疫反应。

Recurrences occurred in eight evaluable patients and were unrelated to the treatment arm.

在可评估的患者中，有八名患者出现了复发，这与治疗组无关。

No patients died during the study because of their disease.

在研究期间，没有患者因疾病死亡。

Conclusions

The reduced-dose FRα vaccine is as effective as the original dose and does not require CP to generate maximal immunity.

减量的FRα疫苗与原剂量疫苗一样有效，并且不需要使用CP就能产生最大免疫反应。

These findings may inform the design of trials testing efficacy in triple-negative breast cancer or other cancers.

这些发现可能为设计在三阴性乳腺癌或其他癌症中测试疗效的试验提供信息。