肿瘤溶解物、颗粒负载的树突状细胞（TLPLDC）疫苗是通过体外成熟自体树突状细胞（DCs）与装载自体肿瘤溶解物（TL）的酵母细胞壁颗粒（YCWPs）进行原位诱导制备的。肿瘤溶解物、仅颗粒（TLPO）疫苗则使用自体TL负载的经硅酸盐包覆的YCWPs进行体内DC负载。本研究报道了这项前瞻性、随机、双盲试验的36个月预先规定的分析结果，研究了TLPO和TLPLDC（±粒细胞增生集落刺激因子（G-CSF））疫苗在高危患者中预防黑色素瘤复发的能力。临床上病情无疾病的Ⅲ/Ⅳ期黑色素瘤患者最初被随机分为TLPLDC与安慰剂组（n=124），随后再随机分为TLPO与TLPLDC组（n=63），2:1的比例。所有患者都是随机并盲目分组的；然而，在第二个随机化方案中，安慰剂对照组被替换为另一种新疫苗；因此，本文中的某些分析反映了两个随机化方案的结合。接受TLPLDC疫苗的患者根据其DC采集方法分成两组（有或无G-CSF预处理）；这并没有随机化。两组之间并未进行标准护理检查点抑制剂的分层对比。对安全性进行评估，采用Kaplan-Meier和log-rank分析比较无疾病（DFS）和总生存（OS）率。在两个随机化过程合并后，共有187名患者被分配到治疗组中：安慰剂组（n=41）、TLPLDC组（n=103）和TLPO组（n=43）。由于两个独立随机化方案中新增患者的加入，各组的分配结果并不反映所有治疗组的同步随机化。TLPLDC疫苗又根据G-CSF的使用进行了 further 分组：无G-CSF的（TLPLDC）组（n=47），和使用G-CSF的（TLPLDC+G）组（n=56）。中位随访时间为35.8个月。只有两名患者经历了与试验相关的≥3级不良事件，分别出现在TLPLDC+G和安慰剂组。DFS分别为27.2%（安慰剂）、55.4%（TLPLDC）、22.9%（TLPLDC+G）和60.9%（TLPO）（p<0.001）。OS分别为62.5%（安慰剂）、93.6%（TLPLDC）、57.7%（TLPLDC+G）和94.6%（TLPO）（p=0.002）。在这个临床试验中，TLPO和不使用G-CSF的TLPLDC疫苗与DFS和OS改善相关。鉴于生产和制造的优势，TLPO疫苗的疗效将在3期试验中得到确认。NCT02301611.©作者（或其雇主）2023.在CC BY-NC下使用。不能用于商业再利用。由BMJ发表。

The tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is made by ex vivo priming matured autologous dendritic cells (DCs) with yeast cell wall particles (YCWPs) loaded with autologous tumor lysate (TL). The tumor lysate, particle only (TLPO) vaccine uses autologous TL-loaded YCWPs coated with silicate for in vivo DC loading. Here we report the 36-month prespecified analyses of this prospective, randomized, double-blind trial investigating the ability of the TLPO and TLPLDC (±granulocyte-colony stimulating factor (G-CSF)) vaccines to prevent melanoma recurrence in high-risk patients.Patients with clinically disease-free stage III/IV melanoma were randomized 2:1 initially to TLPLDC versus placebo (n=124) and subsequently TLPO versus TLPLDC (n=63). All patients were randomized and blinded; however, the placebo control arm was replaced in the second randomization scheme with another novel vaccine; some analyses in this paper therefore reflect a combination of the two randomization schemes. Patients receiving the TLPLDC vaccine were further divided by their method of DC harvest (with or without G-CSF pretreatment); this was not randomized. The use of standard of care checkpoint inhibitors was not stratified between groups. Safety was assessed and Kaplan-Meier and log-rank analyses compared disease-free (DFS) and overall survival (OS).After combining the two randomization processes, a total of 187 patients were allocated between treatment arms: placebo (n=41), TLPLDC (n=103), or TLPO (n=43). The allocation among arms created by the addition of patients from the two separate randomization schemes does not reflect concurrent randomization among all treatment arms. TLPLDC was further divided by use of G-CSF in DC harvest: no G-CSF (TLPLDC) (n=47) and with G-CSF (TLPLDC+G) (n=56). Median follow-up was 35.8 months. Only two patients experienced a related adverse event ≥grade 3, one each in the TLPLDC+G and placebo arms. DFS was 27.2% (placebo), 55.4% (TLPLDC), 22.9% (TLPLDC+G), and 60.9% (TLPO) (p<0.001). OS was 62.5% (placebo), 93.6% (TLPLDC), 57.7% (TLPLDC+G), and 94.6% (TLPO) (p=0.002).The TLPO and TLPLDC (without G-CSF) vaccines were associated with improved DFS and OS in this clinical trial. Given production and manufacturing advantages, the efficacy of the TLPO vaccine will be confirmed in a phase 3 trial.NCT02301611.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.