Barbullushi Kordelia, Rampi Nicolò, Serpenti Fabio, Sciumè Mariarita, Fabris Sonia, De Roberto Pasquale, Fracchiolla Nicola Stefano
Hematology & BMT Unit, Fondazione IRCCS Ca' Granda Policlinico Ospedale Maggiore di Milano, 20122 Milan, Italy.
Department of Oncology and Onco-Hematology, University of Milan, 20122 Milan, Italy.
Cancers (Basel). 2022 Jun 17;14(12):2994. doi: 10.3390/cancers14122994.
Immunotherapy is changing the therapeutic landscape of many hematologic diseases, with immune checkpoint inhibitors, bispecific antibodies, and CAR-T therapies being its greatest expression. Unfortunately, immunotherapy in acute myeloid leukemia (AML) has given less brilliant results up to now, and the only approved drug is the antiCD33 antibody-drug conjugate gemtuzumab ozogamicin. A promising field of research in AML therapy relies on anti-leukemic vaccination to induce remission or prevent disease relapse. In this review, we analyze recent evidence on AML vaccines and their biological mechanisms. The principal proteins that have been exploited for vaccination strategies and have reached clinical experimental phases are Wilm's tumor 1, proteinase 3, and RHAMM. the majority of data deals with WT1-base vaccines, given also the high expression and mutation rates of WT1 in AML cells. Stimulators of immune responses such as TLR7 agonist and interleukin-2 have also proven anti-leukemic activity both in vivo and in vitro. Lastly, cellular vaccines mainly based on autologous or allogeneic off-the-shelf dendritic cell-based vaccines showed positive results in terms of T-cell response and safety, also in elderly patients. Compared to other immunotherapeutic strategies, anti-AML vaccines have the advantage of being a less toxic and a more manageable approach, applicable also to elderly patients with poorer performance status, and may be used in combination with currently available therapies. As for the best scenario in which to use vaccination, whether in a therapeutic, prophylactic, or preemptive setting, further studies are needed, but available evidence points to poorer results in the presence of active or high-burden disease. Given the poor prognosis of relapsed/refractory or high-risk AML, further research is urgently needed to better understand the biological pathways that sustain its pathogenesis. In this setting, research on novel frontiers of immunotherapy-based agents, among which vaccines represent important actors, is warranted to develop new and efficacious strategies to obtain long-term disease control by immune patrolling.
免疫疗法正在改变许多血液系统疾病的治疗格局，免疫检查点抑制剂、双特异性抗体和嵌合抗原受体T细胞（CAR-T）疗法是其最突出的表现形式。不幸的是，到目前为止，急性髓系白血病（AML）的免疫疗法取得的成果并不理想，唯一获批的药物是抗CD33抗体药物偶联物吉妥单抗。AML治疗中一个有前景的研究领域依赖于抗白血病疫苗接种以诱导缓解或预防疾病复发。在这篇综述中，我们分析了关于AML疫苗及其生物学机制的最新证据。已被用于疫苗接种策略并进入临床实验阶段的主要蛋白质有威尔姆斯瘤1、蛋白酶3和透明质酸介导的运动受体（RHAMM）。鉴于WT1在AML细胞中的高表达和突变率，大多数数据都涉及基于WT1的疫苗。免疫反应刺激剂，如Toll样受体7（TLR7）激动剂和白细胞介素-2，在体内和体外均已证明具有抗白血病活性。最后，主要基于自体或现成的异基因树突状细胞疫苗的细胞疫苗在T细胞反应和安全性方面均显示出积极结果，老年患者也是如此。与其他免疫治疗策略相比，抗AML疫苗具有毒性较小、更易于管理的优势，也适用于身体状况较差的老年患者，并且可以与目前可用的疗法联合使用。至于使用疫苗接种的最佳情况，无论是治疗性、预防性还是先发制人设置，都需要进一步研究，但现有证据表明，在存在活动性或高负荷疾病的情况下结果较差。鉴于复发/难治性或高危AML的预后较差，迫切需要进一步研究以更好地了解维持其发病机制所涉及的生物学途径。在这种情况下，基于免疫疗法的新型前沿药物研究是有必要的，其中疫苗是重要组成部分，以开发新的有效策略，通过免疫巡逻实现长期疾病控制。
