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Inoculation Site from a Cutaneous Melanoma Patient Treated with an Allogeneic Therapeutic Vaccine: A Case Report

机译:异基因治疗性疫苗治疗的皮肤黑素瘤患者的接种部位:一例报告

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摘要

We have developed a therapeutic vaccine consisting of a mixture of lethally-irradiated allogeneic cutaneous melanoma cell lines with BCG and GM-CSF as adjuvants. The CSF-470 vaccine is currently being assayed in a Phase II–III trial against medium-dose IFN-α2b. All vaccinated patients immunized intradermally developed large edematous erythema reactions, which then transformed into subcutaneous nodules active for several months. However, vaccine injection sites were not routinely biopsied. We describe the case of a female patient, previously classified as stage III, but who, due to the simultaneous discovery of bone metastases only received one vaccination was withdrawn from the study, and continued her treatment elsewhere. This patient developed a post-vaccination nodule which was surgically removed 7 weeks later, and allowed to analyze the reactivity and immune profiling of the inoculation site. An inflammatory reaction with zones of fibrosis, high irrigation, and brisk lymphoid infiltration, primarily composed of CD8+ and CD20+ lymphocytes, was observed. There were no remaining BCG bacilli, and scarce CD4+ and Foxp3+ T cells were determined. MART-1 Ag was found throughout the vaccination site. CD11c+ Ag presenting cells were either dispersed or forming dense nests. Some CD11c+ cells proliferated; most of them contained intracellular MART-1 Ag, and some interacted with CD8+ lymphocytes. These observations suggest a potent, long-lasting local inflammatory response with recruitment of Ag-presenting cells that incorporate melanoma Ags, probably leading to Ag presentation to naïve T cells.
机译:我们已经开发了一种治疗性疫苗,该疫苗由经致死性辐射的同种异体皮肤黑色素瘤细胞系与BCG和GM-CSF的佐剂组成。目前正在针对中剂量IFN-α2b的II-III期试验中测试CSF-470疫苗。皮内免疫的所有接种疫苗的患者都会出现大的水肿性红斑反应,然后转变为活跃数月的皮下结节。但是,疫苗注射部位没有常规活检。我们描述了一名女性患者的情况,该患者先前被分类为III期,但是由于同时发现了骨转移,该患者仅接受了一次疫苗接种,因此退出了研究,并在其他地方继续进行治疗。该患者出现了疫苗接种后的结节,该结节在7周后被手术切除,并允许分析接种部位的反应性和免疫分布。观察到炎症反应,其中有主要由CD8 + 和CD20 + 淋巴细胞组成的纤维化,高灌注和轻快淋巴样浸润区。没有残留的卡介苗杆菌,并检测到稀缺的CD4 + 和Foxp3 + T细胞。在整个疫苗接种地点发现了MART-1 Ag。 CD11c + Ag呈递细胞分散或形成致密巢。一些CD11c + 细胞增殖;其中大多数含有细胞内的MART-1 Ag,有些与CD8 + 淋巴细胞相互作用。这些观察结果表明,通过掺入掺入黑色素瘤Ag的Ag呈递细胞,可以产生强效,持久的局部炎症反应,可能导致Ag呈递至幼稚的T细胞。

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