Morandi Fabio, Sabatini Federica, Podestà Marina, Airoldi Irma
Laboratorio Cellule Staminali Post-Natali e Terapie Cellulari, Istituto Giannina Gaslini (Istituto di Ricerca e Cura a Carattere Scientifico-IRCCS), Via G. Gaslini 5, 16147 Genova, Italy.
Vaccines (Basel). 2021 Jan 13;9(1):43. doi: 10.3390/vaccines9010043.
Neuroblastoma is the most common extracranial pediatric solid tumor with a heterogeneous clinical course, ranging from spontaneous regression to metastatic disease and death, irrespective of intensive chemotherapeutic regimen. On the basis of several parameters, children affected by neuroblastoma are stratified into low, intermediate and high risk. At present, more than 50% of high-risk patients with metastatic spread display an overall poor long-term outcome also complicated by devastating long-term morbidities. Thus, novel and more effective therapies are desperately needed to improve lifespan of high-risk patients. In this regard, adoptive cell therapy holds great promise and several clinical trials are ongoing, demonstrating safety and tolerability, with no toxicities. Starting from the immunological and clinical features of neuroblastoma, we here discuss the immunotherapeutic approaches currently adopted for high-risk patients and different innovative therapeutic strategies currently under investigation. The latter are based on the infusion of natural killer (NK) cells, as support of consolidation therapy in addition to standard treatments, or chimeric antigen receptor (CAR) T cells directed against neuroblastoma associated antigens (e.g., disialoganglioside GD2). Finally, future perspectives of adoptive cell therapies represented by γδ T lymphocyes and CAR NK cells are envisaged.
神经母细胞瘤是最常见的儿童颅外实体瘤，临床病程具有异质性，从自发消退到转移性疾病和死亡，无论化疗方案强度如何。根据几个参数，患神经母细胞瘤的儿童被分为低、中、高风险组。目前，超过50%发生转移的高危患者总体长期预后较差，还伴有严重的长期并发症。因此，迫切需要新的、更有效的治疗方法来提高高危患者的寿命。在这方面，过继性细胞疗法具有很大的前景，并且正在进行多项临床试验，证明了其安全性和耐受性，且无毒性。从神经母细胞瘤的免疫学和临床特征出发，我们在此讨论目前针对高危患者采用的免疫治疗方法以及目前正在研究的不同创新治疗策略。后者基于输注自然杀伤（NK）细胞，作为标准治疗之外巩固治疗的支持，或针对神经母细胞瘤相关抗原（如双唾液酸神经节苷脂GD2）的嵌合抗原受体（CAR）T细胞。最后，设想了以γδ T淋巴细胞和CAR NK细胞为代表的过继性细胞疗法的未来前景。
