Abstract：
Tumor-associated antigens (TAAs) are potential targets for T cell-based immunotherapy approaches in cutaneous melanoma. BNT111, an investigational lipoplex-formulated mRNA-based therapeutic cancer vaccine encoding melanoma TAAs NY-ESO-1, tyrosinase, MAGE-A3, and TPTE, is undergoing clinical testing in adults. Expression of these TAAs in pediatric melanoma is unclear but is a prerequisite for feasibility of this treatment approach in children with melanoma. Our main objective was to characterize expression of those TAAs in pediatric melanomas compared to control cohorts. In this retrospective case control study, protein and transcript expression of NY-ESO-1, tyrosinase, MAGE-A3, and TPTE were analyzed in a cohort of 25 pediatric melanomas, 31 melanomas of young adults, 29 adult melanomas, and 30 benign melanocytic nevi in children using immunohistochemical staining and digital pathology (QuPath) and reverse transcription quantitative PCR. Based on IHC analysis, pediatric melanomas expressed tyrosinase (100.0%), TPTE (44.0%), MAGE-A3 (12.0%), and NY-ESO-1 (8.0%). Young adult melanomas expressed tyrosinase (96.8%), NY-ESO-1 (19.4%), MAGE-A3 (19.4%), and TPTE (3.2%). Adult melanomas expressed tyrosinase (86.2%), MAGE-A3 (75.9%), NY-ESO-1 (48.3%), and TPTE (48.3%). Childhood melanocytic nevi only expressed tyrosinase (93.3%). Expression prevalence of individual TAAs did not differ between subtypes of pediatric melanoma, and no association with prognosis was found. All four TAAs were expressed in pediatric melanoma, albeit NY-ESO-1 and MAGE-A3 to a lesser extent than in adult melanoma. These data support the possibility of investigating vaccines targeting these TAAs for the treatment of pediatric melanoma.
摘要：
肿瘤相关抗原（TAA）是皮肤黑色素瘤中基于T细胞的免疫治疗方法的潜在靶标。BNT111，一种研究性脂质复合物配制的基于mRNA的治疗性癌症疫苗，编码黑色素瘤TAAsNY-ESO-1，酪氨酸酶，MAGE-A3和TPTE,正在成人中接受临床试验。这些TAA在小儿黑色素瘤中的表达尚不清楚，但这是该治疗方法在儿童黑色素瘤中可行性的先决条件。我们的主要目标是表征与对照组相比，这些TAA在小儿黑色素瘤中的表达。在这项回顾性病例对照研究中，NY-ESO-1、酪氨酸酶、MAGE-A3和TPTE在25例小儿黑色素瘤的队列中进行了分析，31年轻人的黑色素瘤，29个成人黑色素瘤，30例儿童良性黑素细胞痣采用免疫组化染色、数字病理(QuPath)和逆转录定量PCR。基于IHC分析,小儿黑色素瘤表达酪氨酸酶（100.0％），TPTE（44.0%），MAGE-A3（12.0%），和NY-ESO-1（8.0%）。年轻成人黑色素瘤表达酪氨酸酶（96.8%），NY-ESO-1（19.4%），MAGE-A3（19.4%），和TPTE（3.2%）。成人黑色素瘤表达酪氨酸酶（86.2%），MAGE-A3（75.9%），NY-ESO-1（48.3%），和TPTE（48.3％）。儿童黑素细胞痣仅表达酪氨酸酶（93.3％）。个别TAA的表达患病率在小儿黑色素瘤的亚型之间没有差异，未发现与预后相关。所有四种TAAs都在小儿黑色素瘤中表达，尽管NY-ESO-1和MAGE-A3的程度低于成人黑色素瘤。这些数据支持研究靶向这些TAA的疫苗用于治疗小儿黑色素瘤的可能性。
