cancer vaccine

癌症疫苗
  • 文章类型: Journal Article
    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。
    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.
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  • 文章类型: Case Reports
    检查点抑制剂(CIs)现在是晚期非小细胞肺癌(NSCLC)的标准治疗方法;然而,与单用铂类化疗相比,只有少数接受aCI治疗的患者显示出临床获益,无论程序性细胞死亡配体1(PD-L1)表达水平如何。我们描述了一例晚期预处理的鳞状NSCLC患者的持久肿瘤反应和疾病稳定的病例,给予由纳武单抗组成的维持治疗。多西他赛,和雷莫珠单抗联合同种异体细胞癌症疫苗viagenpumatucel-L,为期28个月。我们的案例表明,用于使肿瘤对检查点抑制敏感的组合策略,即使是对现有治疗难以治疗的患者,可能会提高疗效。
    Checkpoint inhibitors (CIs) are now standard of care for late-stage non-small-cell lung cancer (NSCLC); however, only a minority of patients treated with a CI show clinical benefit compared to platinum-based chemotherapy alone, regardless of programmed cell death ligand 1 (PD-L1) expression levels. We describe a case of durable tumor response and disease stabilization in a patient with advanced pretreated squamous NSCLC given a maintenance treatment comprised of nivolumab, docetaxel, and ramucirumab combined with the allogeneic cellular cancer vaccine viagenpumatucel-L over a period of 28 months. Our case suggests that combination strategies that serve to sensitize tumors to checkpoint inhibition, even in patients refractory to available treatment, may lead to improved efficacy.
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  • 文章类型: Case Reports
    脑干胶质瘤在成人中并不常见,治疗策略及其结果有限。免疫疗法正在成为治疗这些神经胶质瘤的一种有前途的新方法。这里,我们报道了首例接受放疗和自体福尔马林固定肿瘤疫苗(AFTV)联合治疗的脑干胶质瘤.一名32岁的男子出现左侧面部麻木和右侧偏瘫,被转介给我们部门.MRI及开放活检提示脑干胶质瘤,他被明确诊断为异柠檬酸脱氢酶1-突变型弥漫性星形细胞瘤WHOII级。三个月后,他接受了立体定向放射治疗,然后接受了AFTV治疗。联合治疗后42个月进行的MRI显示肿瘤体积减少了91%,并维持了5年的回归。因此,放疗和免疫治疗的联合治疗可能是治疗脑干胶质瘤的一种有希望的替代方法.
    Brainstem gliomas are not common in adults, and the treatment strategies and their outcomes are limited. Immunotherapy is emerging as a promising new modality for the treatment of these gliomas. Here, we report the first case of brainstem glioma treated with a combination of radiotherapy and autologous formalin-fixed tumor vaccine (AFTV). A 32-year-old man presented with left facial numbness and right hemiparesis, and was referred to our department. MRI and open biopsy indicated brainstem glioma, and he was specifically diagnosed with isocitrate dehydrogenase 1-mutant diffuse astrocytoma of WHO grade II. He was treated with stereotactic radiotherapy followed by AFTV three months later. MRI conducted at 42 months after the combination therapy showed a 91% decrease in tumor volume, and the regression was maintained for 5 years. Thus, combination treatment with radiotherapy and immunotherapy may prove to be a promising alternative for the treatment of brainstem glioma.
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