多特异性 T 细胞接合支架已成为治疗血液恶性肿瘤的有效抗癌疗法。需要调节癌细胞靶向并提供个性化、多特异性免疫治疗的方法。在这里，我们报告了一种模块化、分裂抗体样方法，由用互补吗啉代寡核苷酸（MORF）修饰的 Fab' 片段组成。我们合成了一个 B 细胞靶向 Fab'-MORF1 缀合物库，该库通过 Watson-Crick 碱基配对杂交与互补的 T 细胞接合 Fab'-MORF2 缀合物进行自组装。我们恰当地将我们的技术命名为多抗原 T 细胞杂交仪 (MATCH)。使用 MATCH，利用四种 B 细胞抗原靶标实现癌症特异性 T 细胞募集：CD20、CD38、BCMA 和 SLAMF7。产生了各种恶性 B 细胞系的抗原表达谱，并利用这些不同的谱，在体外对淋巴瘤、白血病和多发性骨髓瘤细胞系实现了细胞特异性 T 细胞激活。 T 细胞再攻击实验证明了 MATCH 的模块化方法，即使用癌症抗原特异性 Fab'-MORF1 缀合物依次激活针对三种不同癌症的相同 T 细胞群。此外，通过使用 CD20 导向的 MATCH 疗法治疗人类非霍奇金淋巴瘤的异种移植小鼠模型，MATCH 的功效在体内得到了证明。在初步研究中，与盐水对照相比，单剂量的 MATCH 可以使所有治疗小鼠长期存活。在第二个体内模型中，当 T 细胞与靶细胞比例为 5:1 的 MATCH 治疗小鼠与更高和更高比例的小鼠相比，显着延迟了疾病的发作时，收集了有关最佳 T 细胞与靶细胞比例的见解。较低的比率。

Multispecific T-cell-engaging scaffolds have emerged as effective anticancer therapies for the treatment of hematological malignancies. Approaches that modulate cancer cell targeting and provide personalized, multispecific immunotherapeutics are needed. Here, we report on a modular, split antibody-like approach consisting of Fab' fragments modified with complementary morpholino oligonucleotides (MORFs). We synthesized a library of B-cell-targeting Fab'-MORF1 conjugates that self-assemble, via a Watson-Crick base pairing hybridization, with a complementary T-cell-engaging Fab'-MORF2 conjugate. We aptly titled our technology multiantigen T-cell hybridizers (MATCH). Using MATCH, cancer-specific T-cell recruitment was achieved utilizing four B-cell antigen targets: CD20, CD38, BCMA, and SLAMF7. The antigen expression profiles of various malignant B-cell lines were produced, and using these distinct profiles, cell-specific T-cell activation was attained on lymphoma, leukemia, and multiple myeloma cell lines in vitro. T-cell rechallenge experiments demonstrated the modular approach of MATCH by sequentially activating the same T-cell cohort against three different cancers using cancer antigen-specific Fab'-MORF1 conjugates. Furthermore, MATCH's efficacy was demonstrated in vivo by treating xenograft mouse models of human non-Hodgkin's lymphoma with CD20-directed MATCH therapy. In the pilot study, a single dose of MATCH allowed for long-term survival of all treated mice compared to saline control. In a second in vivo model, insights regarding optimal T-cell-to-target cell ratio were gleaned when a ratio of 5:1 T-cell-to-target cell MATCH-treated mice significantly delayed the onset of disease compared to higher and lower ratios.