There is a need to improve outcomes for patients with recurrent and/or refractory hematological malignancies. Immunotherapy holds the promise to meet this need, because it does not rely on the cytotoxic mechanism of conventional therapies. Among different forms of immunotherapy, redirecting T cells to hematological malignancies with bispecific antibodies (BsAbs) is an attractive strategy. BsAbs are an "off-the-shelf" product that is easily scalable in contrast to adoptive T-cell therapies. Among these, the bispecific T-cell engager blinatumomab has emerged as the most successful BsAb to date. It consists of 2 single-chain variable fragments specific for CD19 present on B-cell malignancies and CD3 expressed on almost all T cells. Blinatumomab has shown potent antitumor activity as a single agent, particularly for acute lymphoblastic leukemia, resulting in its US Food and Drug Administration approval. However, although successful in inducing remissions, these are normally short-lived, with median response durations of <1 year. Nevertheless, the success of blinatumomab has reinvigorated the BsAb field, which is bustling with preclinical and clinical studies for not only B-cell-derived lymphoblastic leukemia and lymphoma but also acute myeloid leukemia and multiple myeloma. Here, we will review the successes and challenges of T-cell-targeted BsAbs for the immunotherapy of hematological malignancies with special focus on conducted clinical studies and strategies to improve their efficacy.

中文翻译：

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使用双特异性抗体将 T 细胞重定向至血液恶性肿瘤

需要改善患有复发性和/或难治性血液恶性肿瘤的患者的结果。免疫疗法有望满足这一需求，因为它不依赖传统疗法的细胞毒性机制。在不同形式的免疫疗法中，利用双特异性抗体 (BsAb) 将 T 细胞重定向至血液恶性肿瘤是一种颇具吸引力的策略。BsAb 是一种“现成”产品，与过继性 T 细胞疗法相比，易于扩展。其中，双特异性 T 细胞接合器 blinatumomab 已成为迄今为止最成功的 BsAb。它由 2 个单链可变片段组成，对 B 细胞恶性肿瘤上存在的 CD19 和几乎所有 T 细胞上表达的 CD3 具有特异性。Blinatumomab 作为单一药物已显示出强大的抗肿瘤活性，特别是对于急性淋巴细胞白血病，因此获得了美国食品和药物管理局的批准。然而，尽管成功诱导缓解，但这些缓解通常是短暂的，中位缓解持续时间<1年。尽管如此，blinatumomab 的成功重振了 BsAb 领域的活力，该领域不仅针对 B 细胞源性淋巴细胞白血病和淋巴瘤，而且还针对急性髓系白血病和多发性骨髓瘤开展临床前和临床研究。在这里，我们将回顾 T 细胞靶向双特异性抗体用于血液恶性肿瘤免疫治疗的成功和挑战，特别关注已进行的临床研究和提高其疗效的策略。