TCR-JANUS 衔接蛋白实现双特异性靶向以克服 TCR-T 细胞治疗中的肿瘤异质性
TCR-JANUS engager proteins enable bispecific targeting to overcome tumor heterogeneity in TCR-T cell therapy.
基于 T 细胞受体(TCR)的免疫疗法受限于肿瘤抗原异质性,后者常导致复发。
英文原题:Trop2-expression in primary vulvar squamous cell carcinoma.
Trop2的广泛表达使其成为Trop2导向抗体药物偶联物(ADC)sacituzumab govitecan(SG)的一个有趣的潜在靶点。需要评估SG在VSCC中的安全性和有效性的临床试验。
外阴鳞状细胞癌(VSCC)是一种罕见的恶性肿瘤,但发病率正在增加。治疗选择通常限于手术和放(化)疗。缺乏新的治疗策略。滋养层细胞表面抗原2(Trop2)是一种正在不同肿瘤实体中使用的新靶点。当前研究的目的是评估Trop2在VSCC中的表达。
我们构建了一个下一代组织微阵列(ngTMA),纳入2000年至2021年间在埃尔朗根大学医院妇产科接受治疗的原发性VSCC女性患者,分析Trop2的表达。进一步分析了临床病理特征:肿瘤分期、区域淋巴结状态、静脉、淋巴管和神经鞘侵犯、浸润深度、分级、p16/p53亚型以及TIL(肿瘤浸润淋巴细胞)。
共纳入217名女性。Trop2在VSCC中100%表达。根据Trop2的中位数(H-score:279),将女性分为“低表达”和“高表达”两组。p16+/p53-是Trop2高表达患者中最常见的p16/p53亚型。Trop2在VSCC女性中倾向于更好的预后,因此对最常见的p16-/p53+亚型无临床影响。
OBJECTIVES: Vulvar squamous cell carcinoma (VSCC) is a rare malignant disease but with increasing incidence. Therapeutic options are generally limited to surgery and radio-(chemo)therapy. New strategies for therapy are lacking. Trophoblast cell surface antigen 2 (Trop2) is a new target being used in different tumor entities. The purpose of the current research is to assess the expression of Trop2 in VSCC. METHODS: We constructed a next generation tissue micro array (ngTMA) including women with primary VSCC treated between 2000 and 2021 at the Department of Gynecology and Obstetrics, Erlangen University Hospital analyzing the expression of Trop2. Further clinicopathologic characteristics were analyzed: tumor stage, regional lymph node-status, venous-, lymphatic- and perineural sheath invasion, depth of invasion, grading, p16/p53 subtype and tumor infiltration lymphocytes. RESULTS: A total of 217 women were included. Trop2 was expressed in 100 % of VSCC. Women were split in two groups, the "low expression" and the "high expression" groups, according to the median of Trop2 (H-score: 279). p16+/p53- is the most common p16/p53 subtype in patients with high Trop2 expression. Trop2 favored a better prognosis in women with VSCC, hence not clinically impactful for the most common p16-/p53+ subtype. CONCLUSION: The ubiquitous expression of Trop2 makes it an interesting potential target for the Trop2 directed antibody drug conjugate (ADC) sacituzumab govitecan (SG). Clinical trials evaluating the safety and effectiveness of SG in VSCC are needed.
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