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首页> 外文期刊>The Journal of Immunology: Official Journal of the American Association of Immunologists >Targeting melanoma cells with human high molecular weight-melanoma associated antigen-specific antibodies elicited by a peptide mimotope: functional effects.
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Targeting melanoma cells with human high molecular weight-melanoma associated antigen-specific antibodies elicited by a peptide mimotope: functional effects.

机译:用人高分子量-黑色素瘤相关抗原特异性抗体(由肽模拟表位引发)靶向黑色素瘤细胞:功能作用。

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摘要

Human high molecular weight-melanoma associated Ag (HMW-MAA) mimics have been shown to elicit HMW-MAA-specific humoral immune responses that appear to be clinically beneficial. This finding has stimulated interest in characterizing the mechanism(s) underlying the ability of the elicited Abs to exert an anti-tumor effect. To address this question, in the present study, we have generated HMW-MAA-specific Abs by sequentially immunizing rabbits with the peptide P763.74, which mimics the HMW-MAA determinant recognized by mAb 763.74, and with HMW-MAA(+) melanoma cells. HMW-MAA-specific Abs isolated from immunized rabbits mediated cell-dependent cytotoxicity but did not mediate complement-dependent cytotoxicity of HMW-MAA(+) melanoma cells. These Abs also effectively inhibited spreading, migration and Matrigel invasion of HMW-MAA(+) melanoma cells. Besides contributing to our understanding of the role of HMW-MAA in the biology of melanoma cells, these results suggest that both immunological and nonimmunological mechanisms underlie the beneficial clinical effects associated with the induction of HMW-MAA-specific Abs in melanoma patients immunized with a HMW-MAA mimic.
机译:人类高分子量黑素瘤相关的银(HMW-MAA)模拟物已显示出引起HMW-MAA特异性的体液免疫反应,在临床上似乎是有益的。这一发现激发了人们对表征引起的Abs发挥抗肿瘤作用的能力的机制的兴趣。为了解决这个问题,在本研究中,我们通过用模拟单克隆抗体763.74识别的HMW-MAA决定簇的肽P763.74和HMW-MAA(+)顺序免疫兔,从而产生了HMW-MAA特异性抗体。黑色素瘤细胞。从免疫兔中分离出的HMW-MAA特异性抗体可介导细胞依赖性细胞毒性,但不介导HMW-MAA(+)黑色素瘤细胞的补体依赖性细胞毒性。这些抗体还有效抑制HMW-MAA(+)黑色素瘤细胞的扩散,迁移和基质胶侵袭。这些结果除了有助于我们了解HMW-MAA在黑素瘤细胞生物学中的作用外,还表明免疫学和非免疫学机制均是与HMV-MAA特异性Abs免疫接种黑素瘤患者相关的有益临床作用的基础。 HMW-MAA模拟。

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