Inability to immunize patients with metastatic melanoma using plasmid DNA encoding the gp100 melanoma-melanocyte antigen
Inability to immunize patients with metastatic melanoma using plasmid DNA encoding the gp100 melanoma-melanocyte antigen
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DOI：
10.1089/104303403765255110
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发表时间：
2003-05-01
影响因子：
4.2
通讯作者：
White, DE
中科院分区：
文献类型：
--
作者：
Rosenberg, SA;Yang, JC;White, DE
质粒DNA免疫代表了一种理论上有吸引力的方法来增加T细胞对癌症抗原的反应。我们给22例转移性黑色素瘤患者注射了编码gp100黑色素瘤-黑色素细胞分化抗原的质粒DNA，并评估了免疫和临床反应。患者随机接受质粒DNA皮下注射（n = 10）或肌肉注射（n = 12）。1例患者（4.5%）表现出几个亚厘米皮肤结节的部分缓解。其他患者均为进行性疾病。在免疫前后有细胞的13例患者中，没有患者在体外增强试验中表现出抗gp100细胞反应的证据。同样的实验能够证明编码gp100或gp100肽的禽痘病毒免疫后的免疫前体。因此，我们无法证明编码“自我”非突变gp100肿瘤抗原的质粒DNA有显著的临床或免疫应答。
Immunization with plasmid DNA represents a theoretically attractive method for increasing T cell responses against cancer antigens. We administered plasmid DNA encoding the gp100 melanoma-melanocyte differentiation antigen to 22 patients with metastatic melanoma and evaluated immunologic and clinical responses. Patients were randomized to receive plasmid DNA either intradermally (n = 10) or intramuscularly (n = 12). One patient (4.5%) exhibited a partial response of several subcentimeter cutaneous nodules. All other patients had progressive disease. Of 13 patients with cells available before and after immunization, no patient exhibited evidence of the development of anti-gp100 cell responses using in vitro boost assays. The same assays were capable of demonstrating immunologic precursors after immunization with fowl poxvirus encoding gp100 or with gp100 peptides. We were thus unable to demonstrate significant clinical or immunologic responses to plasmid DNA encoding the "self" nonmutated gp100 tumor antigen.