肿瘤细胞治疗研究
英文原题：Anti-GD2 Antibody Dinutuximab Beta and Low-Dose Interleukin 2 After Haploidentical Stem-Cell Transplantation in Patients With Relapsed Neuroblastoma: A Multicenter, Phase I/II Trial.
rHR-NB患者接受haplo-SCT后的DB治疗是可行的，诱导GvHD的风险低，并可实现长期缓解，这很可能归因于供者来源效应细胞抗神经母细胞瘤活性的增强。
复发高危神经母细胞瘤（rHR-NB）患者预后不良。我们假设，通过移植单倍体相合干细胞（haplo-SCT），利用NK 细胞的细胞毒性功能及其被抗GD2抗体dinutuximab beta（DB）激活，可以诱导移植物抗神经母细胞瘤效应。这项I/II期试验评估了rHR-NB患者在接受haplo-SCT后使用DB联合皮下白细胞介素-2（scIL2）免疫治疗的安全性、可行性和结局。
1-21岁的患者接受T/B细胞去除的单倍体SCT，随后进行DB和scIL2。主要终点“治疗成功”包括接受六个周期、在试验治疗结束后180天存活且无疾病进展、不可接受的毒性、急性移植物抗宿主病（GvHD）≥3级或广泛性慢性GvHD的患者。
70 例患者接受筛选，68 例符合免疫治疗条件。DB 周期中位数为 6（范围，1-9）。scIL2 周期中位数为 3（1-6）。37 例患者（54.4%）达到主要终点。中位观察时间为 7.8 年。自试验治疗开始起的 5 年无事件生存（EFS）率和总生存率分别为 43%（95% CI，31 至 55）和 53%（95% CI，41 至 65）。免疫治疗前达到完全缓解（CR；52%；95% CI，31 至 69）或部分缓解（44%；95% CI，27 至 60）的患者的 5 年 EFS 显著优于无缓解/混合缓解/疾病进展的患者（13%；95% CI，1 至 42；P = .026）。43 例 haplo-SCT 后有疾病证据的患者的总体缓解率为 51%（22 例患者），其中 15 例达到 CR（35%）。2 例患者分别发生 2 级和 3 级 GvHD。未发生非预期不良事件。
PURPOSE: Patients with relapsed high-risk neuroblastoma (rHR-NB) have a poor prognosis. We hypothesized that graft-versus-neuroblastoma effects could be elicited by transplantation of haploidentical stem cells (haplo-SCT) exploiting cytotoxic functions of natural killer cells and their activation by the anti-GD2 antibody dinutuximab beta (DB). This phase I/II trial assessed safety, feasibility, and outcomes of immunotherapy with DB plus subcutaneous interleukin-2 (scIL2) after haplo-SCT in patients with rHR-NB. METHODS: Patients age 1-21 years underwent T-/B-cell-depleted haplo-SCT followed by DB and scIL2. The primary end point 'success of treatment' encompassed patients receiving six cycles, being alive 180 days after end of trial treatment without progressive disease, unacceptable toxicity, acute graft-versus-host-disease (GvHD) ≥grade 3, or extensive chronic GvHD. RESULTS: Seventy patients were screened, and 68 were eligible for immunotherapy. Median number of DB cycles was 6 (range, 1-9). Median number of scIL2 cycles was 3 (1-6). The primary end point was met by 37 patients (54.4%). Median observation time was 7.8 years. Five-year event-free survival (EFS) and overall survival from start of trial treatment were 43% (95% CI, 31 to 55) and 53% (95% CI, 41 to 65), respectively. Five-year EFS among patients in complete remission (CR; 52%; 95% CI, 31 to 69) or partial remission (44%; 95% CI, 27 to 60) before immunotherapy were significantly better compared with patients with nonresponse/mixed response/progressive disease (13%; 95% CI, 1 to 42; P = .026). Overall response rate in 43 patients with evidence of disease after haplo-SCT was 51% (22 patients), with 15 achieving CR (35%). Two patients developed GvHD grade 2 and 3 each. No unexpected adverse events occurred. CONCLUSION: DB therapy after haplo-SCT in patients with rHR-NB is feasible, with low risk of inducing GvHD, and results in long-term remissions likely attributable to increased antineuroblastoma activity by donor-derived effector cells.
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