Nature Cancer：靶向TRBC2的ADC药物，治疗T细胞癌

Core Viewpoint - The article discusses the challenges and advancements in developing targeted therapies for T-cell cancers, particularly focusing on antibody-drug conjugates (ADCs) that target TRBC2 and TRBC1, which may provide new treatment options for patients with limited survival rates [1][3][6]. Group 1: T-cell Cancer Overview - T-cell leukemia and lymphoma, collectively known as T-cell cancer, see approximately 100,000 new patients globally each year [1]. - The 5-year survival rate for adult patients with relapsed T-cell cancer ranges from 7% to 38%, highlighting the limited treatment options available compared to B-cell cancers [1]. Group 2: Antibody-Drug Conjugates (ADCs) - ADCs are a novel class of targeted drugs composed of antibodies, cytotoxic agents, and linkers, designed to selectively deliver cytotoxic molecules to tumor cells while sparing healthy cells [1]. - While ADCs have shown significant success in treating solid tumors and hematologic malignancies, developing ADCs for T-cell cancers poses unique challenges due to the need to selectively target malignant T-cells without harming normal T-cells [1]. Group 3: Research Developments - A study published by Suman Paul’s team at Johns Hopkins University developed a TRBC2-targeting ADC for T-cell cancer treatment, demonstrating specific cytotoxic effects on TRBC2-positive cancer cells in vitro and in mouse models [2][6]. - The research indicates that targeting TRBC2 could provide a promising and ready-to-use treatment option for T-cell cancer patients [6]. Group 4: TRBC1-targeting ADCs - Another study from the same team confirmed that CAR-T cells targeting TRBC1 could inadvertently kill normal TRBC1+ T-cells, leading to poor treatment responses [7]. - To address this issue, the team developed a TRBC1-targeting ADC that effectively treats T-cell cancer in vitro and in mouse models, suggesting it may offer an optimal targeting strategy for TRBC1 [8].