在这项研究中，我们测试了一种新方法，将通常与乳腺癌相关的生物标志物“重新利用”，用于治疗黑色素瘤。 HER2/neu 是乳腺癌中一种特征明确的生物标志物，有效的抗 HER2/neu 疗法很容易获得。我们构建了编码 c-erb-B2 的慢病毒，c-erb-B2 是 HER2/neu 的动物（大鼠）同源物。这用于体外转染 B16 黑色素瘤，用于原位临床前小鼠模型，导致大鼠 c-erb-B2 表达作为抗 c-erb-B2 单克隆抗体的新抗原靶标 (7.16.4)。表达c-erb-B2的黑色素瘤被命名为B16/neu。 7.16.4 对 B16/neu 产生统计学显着的体内抗肿瘤反应。这种效应是由 NK 细胞抗体依赖性细胞介导的细胞毒性介导的。为了进一步模拟人类黑色素瘤（表达 < 5% HER2/neu），我们的c-erb-B2编码慢病毒被用来在体内接种幼稚（野生型）B16肿瘤，从而成功表达c-erb-B2。当与 7.16.4 组合时，再次证明了抗肿瘤反应，其中约 40% 的用 c-erb-B2 慢病毒和 7.16.4 治疗的小鼠实现了完全临床反应和长期存活。我们首次展示了一种新策略，将 c-erb-B2 重新用作黑色素瘤的新抗原靶点。我们的研究结果在当代环境中尤其重要，因为新型抗 HER2/neu 抗体药物疗法已显示出更高的疗效。© 2024。作者。

In this study, we tested a novel approach of "repurposing" a biomarker typically associated with breast cancer for use in melanoma. HER2/neu is a well characterized biomarker in breast cancer for which effective anti-HER2/neu therapies are readily available. We constructed a lentivirus encoding c-erb-B2, an animal (rat) homolog to HER2/neu. This was used to transfect B16 melanoma in vitro for use in an orthotopic preclinical mouse model, which resulted in expression of rat c-erb-B2 as a neoantigen target for anti-c-erb-B2 monoclonal antibody (7.16.4). The c-erb-B2-expressing melanoma was designated B16/neu. 7.16.4 produced statistically significant in vivo anti-tumor responses against B16/neu. This effect was mediated by NK-cell antibody-dependent cell-mediated cytotoxicity. To further model human melanoma (which expresses < 5% HER2/neu), our c-erb-B2 encoding lentivirus was used to inoculate naïve (wild-type) B16 tumors in vivo, resulting in successful c-erb-B2 expression. When combined with 7.16.4, anti-tumor responses were again demonstrated where approximately 40% of mice treated with c-erb-B2 lentivirus and 7.16.4 achieved complete clinical response and long-term survival. For the first time, we demonstrated a novel strategy to repurpose c-erb-B2 as a neoantigen target for melanoma. Our findings are particularly significant in the contemporary setting where newer anti-HER2/neu antibody-drug therapies have shown increased efficacy.© 2024. The Author(s).