Paredes-Moscosso Solange R, Nathwani Amit C
Centro de Genética y Biología Molecular, Instituto de Investigación, Facultad de Medicina Humana, Universidad de San Martín de Porres, Lima, Peru.
Facultad de Ciencias de la Salud, Universidad Peruana de Ciencias Aplicadas, Lima, Peru.
Front Oncol. 2024 Dec 20;14:1429330. doi: 10.3389/fonc.2024.1429330. eCollection 2024.
Various therapeutic strategies have been developed to treat Pancreatic Cancer (PaCa). Unfortunately, most efforts have proved unfruitful, as the poor prognosis observed in this disease has only attained little improvement in the past 40 years. Recently, deeper understanding of the immune system and its interaction with malignant tumors have allowed significant advances in immunotherapy. Consistent with this, some of the most promising approaches are those that involve T-cell redirection to the tumor site, such as bispecific T-cell engagers (BiTEs). These recombinant antibodies bridge cytotoxic T-cells to tumor cells, inducing target cell-dependent polyclonal T-cell activation/proliferation, which in turn results in elimination of bound tumor cells. Blinatumomab, an anti-CD19 BiTE, received FDA approval in 2014 for Precursor B-cell Acute Lymphoblastic Leukemia. In the past decade, it has demonstrated impressive clinical benefit in patients with B-cell leukemias; and other T-cell engagers have been FDA-approved for hematological malignancies and other diseases, yet limited effect has been observed with other BiTEs against solid cancers, including PaCa. Nevertheless, on May 2024, Tarlatamab, an anti-DLL3 BiTE was approved by the FDA for extensive small cell lung cancer, becoming the first BiTE for solid tumors. In this review, the generation of BiTEs, therapeutic features, manufacturing issues as well as the remaining challenges and novel strategies of BiTE therapy in the context of PaCa, including the lessons we can learn from the use of BiTEs on other types of cancer will be explored.
人们已经开发出各种治疗策略来治疗胰腺癌（PaCa）。不幸的是，大多数努力都没有成效，因为在这种疾病中观察到的不良预后在过去40年里只得到了很小的改善。最近，对免疫系统及其与恶性肿瘤相互作用的更深入了解推动了免疫疗法的重大进展。与此一致的是，一些最有前景的方法是那些涉及将T细胞重定向到肿瘤部位的方法，比如双特异性T细胞衔接器（BiTEs）。这些重组抗体将细胞毒性T细胞与肿瘤细胞连接起来，诱导靶细胞依赖性多克隆T细胞激活/增殖，进而导致结合的肿瘤细胞被清除。抗CD19 BiTE药物blinatumomab于2014年获得美国食品药品监督管理局（FDA）批准，用于治疗前体B细胞急性淋巴细胞白血病。在过去十年中，它在B细胞白血病患者中显示出令人瞩目的临床益处；其他T细胞衔接器已获得FDA批准用于治疗血液系统恶性肿瘤和其他疾病，但针对包括PaCa在内的实体癌的其他BiTEs疗效有限。尽管如此，2024年5月，抗DLL3 BiTE药物tarlatamab获得FDA批准用于广泛期小细胞肺癌，成为首个获批用于实体瘤的BiTE。在这篇综述中，将探讨BiTEs的产生、治疗特性、生产问题，以及在PaCa背景下BiTE治疗的剩余挑战和新策略，包括我们可以从在其他类型癌症中使用BiTEs中学到的经验教训。
