肿瘤细胞治疗研究
英文原题：Recent advances in monoclonal antibody development for treatment of B-cell acute lymphoblastic leukemia.
靶向 CD19、CD20 和 CD22 的单克隆抗体（mAb）疗法彻底改变了 B-ALL 的治疗，其通过调动免疫机制清除白血病细胞，从而带来精准性并降低全身毒性。
靶向CD19、CD20和CD22的单克隆抗体（mAb）疗法彻底改变了B细胞急性淋巴细胞白血病（B-ALL）的治疗，通过调动免疫机制清除白血病细胞，实现精准治疗并降低全身毒性。本综述汇总了PubMed、Web of Science及ClinicalTrials.gov（2000–2024年）的文献，重点讨论临床结局和耐药机制。双特异性T细胞衔接器（如贝林妥欧单抗）和靶向CD22的抗体药物偶联物（如奥加伊妥珠单抗）在复发或难治性疾病中显示出显著疗效。抗体工程进展（如Fc优化、纳米抗体和人源化）可提高肿瘤靶向能力和治疗安全性。持续存在的挑战包括抗原逃逸、基质介导的耐药及治疗相关毒性。将mAb与CAR-T细胞或免疫检查点抑制剂联合的策略，有望克服耐药通路。人工智能和深度学习等新兴技术正在改变抗体设计，可预测表位结合、实现从头蛋白质工程并简化亲和力成熟。这些创新加速了下一代疗法的开发，凸显B-ALL精准免疫治疗不断发展的潜力。
Monoclonal antibody (mAb)-based therapies targeting CD19, CD20, and CD22 have revolutionized B-ALL treatment, offering precision and reduced systemic toxicity by engaging immune mechanisms to eliminate leukemic cells. This review synthesizes literature from PubMed, Web of Science, and ClinicalTrials.gov (2000-2024), focusing on clinical outcomes and resistance mechanisms. Bispecific T-cell engagers (e.g. blinatumomab) and CD22-directed antibody-drug conjugates (e.g. inotuzumab ozogamicin) demonstrate robust efficacy in relapsed/refractory disease. Advances in antibody engineering, such as Fc optimization, nanobodies, and humanization, enhance tumor targeting and therapeutic safety. Persistent challenges include antigen escape, stromal-mediated resistance, and treatment-related toxicities. Combinatorial approaches integrating mAbs with CAR-T cells or checkpoint inhibitors show promise in overcoming resistance pathways. Emerging technologies like artificial intelligence and deep learning are transforming antibody design by predicting epitope binding, enabling de novo protein engineering, and streamlining affinity maturation. These innovations accelerate the development of next-generation therapies, underscoring the evolving potential of precision immunotherapy of B-ALL.
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