Scholarlink

<p>Despite the paradigm-shifting success of anti-CD20 monoclonal antibodies like rituximab, limitations such as antigen loss, impaired host immune effector functions, and resistance remain key challenges in non-Hodgkin lymphoma (NHL). Antibody-drug conjugates (ADCs) targeting CD20 represent a promising strategy to overcome these limitations by delivering potent cytotoxic payloads directly to malignant B cells. However, CD20’s slow internalization rate poses a unique challenge for conventional ADC design. This review provides a focused analysis of clinical- and preclinical-stage CD20-directed ADCs, examining how innovative design strategies—including cleavable linkers, membrane-permeable payloads (e.g., MMAE), site-specific conjugation, and novel platforms such as extracellular drug conjugates (EDCs) and immune-stimulating antibody conjugates (ISACs)—are being developed to circumvent the internalization barrier. We critically analyze clinical progress (MRG001 and TRS005), preclinical innovations, and future directions for translating the promise of CD20-directed ADCs into clinical reality for patients with NHL.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

CD20-directed antibody-drug conjugates in non-hodgkin lymphoma: translating preclinical promise into clinical reality

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月13日

查看全文
  • Leila Omidvar,
  • Ali Hussein Mer,
  • Yousef Mirzaei,
  • Mohammad-Reza Sanaye-Pasand,
  • Saeed Jahandideh,
  • Mahmoud Hassani,
  • Meghdad Abdollahpour-Alitappeh

摘要

Despite the paradigm-shifting success of anti-CD20 monoclonal antibodies like rituximab, limitations such as antigen loss, impaired host immune effector functions, and resistance remain key challenges in non-Hodgkin lymphoma (NHL). Antibody-drug conjugates (ADCs) targeting CD20 represent a promising strategy to overcome these limitations by delivering potent cytotoxic payloads directly to malignant B cells. However, CD20’s slow internalization rate poses a unique challenge for conventional ADC design. This review provides a focused analysis of clinical- and preclinical-stage CD20-directed ADCs, examining how innovative design strategies—including cleavable linkers, membrane-permeable payloads (e.g., MMAE), site-specific conjugation, and novel platforms such as extracellular drug conjugates (EDCs) and immune-stimulating antibody conjugates (ISACs)—are being developed to circumvent the internalization barrier. We critically analyze clinical progress (MRG001 and TRS005), preclinical innovations, and future directions for translating the promise of CD20-directed ADCs into clinical reality for patients with NHL.