淋巴惡性腫瘤新免疫療法

淋巴惡性腫瘤新免疫療法

摘要：靶向CD20單克隆抗體立普妥單抗在惡性淋巴瘤中的治療成功，為開發(fā)免疫系統(tǒng)治療提供了原則性的證據(jù)。自從FDA在1997年批準了立普妥單抗，一些新的利用T細胞的能力靶向?qū)拱┘毎牟呗砸渤霈F(xiàn)了。為了反映出這些新的免疫治療途徑的前景，F(xiàn)DAzui近對三種不同機制的新治療方案賦予了“重要技術(shù)突破”的稱號。首先，嵌合抗原受體修飾的T細胞（CAR-T）治療方案對成人和兒童復(fù)發(fā)或難治性急性淋巴白血病（ALL）的治療展現(xiàn)出了希望。第二個，blinatumomab，雙特異性T細胞銜接器（BiTE®）抗體藥物，現(xiàn)在被批準用于治療成人費城染色體缺失型復(fù)發(fā)和/或者難治性記性B淋巴細胞白血病。zui后一個，是單克隆抗體立普妥，針對PD-1免疫檢查點受體具有高親和力，用于治療霍奇金淋巴瘤治療后失敗的自體干細胞移植和藥物brentuximab vedotin治療。在這里，我們回顧了這三種不同的免疫治療平臺的背景和發(fā)展，了解每種治療方案的作用機制來促進了科學的提高，并評估目前的臨床知識，其療效和安全性。我們還討論了將來的治療策略，通過加強改造、生物標志物的選擇、以機制為基礎(chǔ)的聯(lián)合治療方案來提高這些免疫療方法。

Novel immunotherapies in lymphoid malignancies

Abstract

The success of the anti-CD20 monoclonal antibody rituximab in the treatment of lymphoid malignancies provided proof-of-principle for exploiting the immune system therapeutically. Since the FDA approval of rituximab in 1997, several novel strategies that harness the ability of T cells to target cancer cells have emerged. Reflecting on the promising clinical efficacy of these novel immunotherapy approaches, the FDA has recently granted 'breakthrough' designation to three novel treatments with distinct mechanisms. First, chimeric antigen receptor (CAR)-T-cell therapy is promising for the treatment of adult and paediatric relapsed and/or refractory acute lymphoblastic leukaemia (ALL). Second, blinatumomab, a bispecific T-cell engager (BiTE®) antibody, is now approved for the treatment of adults with Philadelphia-chromosome-negative relapsed and/or refractory B-precursor ALL. Finally, the monoclonal antibody nivolumab, which targets the PD-1 immune-checkpoint receptor with high affinity, is used for the treatment of Hodgkin lymphoma following treatment failure with autologous-stem-cell transplantation and brentuximab vedotin. Herein, we review the background and development of these three distinct immunotherapy platforms, address the scientific advances in understanding the mechanism of action of each therapy, and assess the current clinical knowledge of their efficacy and safety. We also discuss future strategies to improve these immunotherapies through enhanced engineering, biomarker selection, and mechanism-based combination regimens.