Immunotherapy using either checkpoint blockade or the adoptive transfer of antitumor lymphocytes has shown effectiveness in treating cancers with high levels of somatic mutations-such as melanoma, smoking-induced lung cancers and bladder cancer-with little effect in other common epithelial cancers that have lower mutation rates, such as those arising in the gastrointestinal tract, breast and ovary^1-7. Adoptive transfer of autologous lymphocytes that specifically target proteins encoded by somatically mutated genes has mediated substantial objective clinical regressions in patients with metastatic bile duct, colon and cervical cancers^8-11. We present a patient with chemorefractory hormone receptor (HR)-positive metastatic breast cancer who was treated with tumor-infiltrating lymphocytes (TILs) reactive against mutant versions of four proteins-SLC3A2, KIAA0368, CADPS2 and CTSB. Adoptive transfer of these mutant-protein-specific TILs in conjunction with interleukin (IL)-2 and checkpoint blockade mediated the complete durable regression of metastatic breast cancer, which is now ongoing for >22 months, and it represents a new immunotherapy approach for the treatment of these patients.

中文翻译：

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对体细胞突变的免疫识别导致转移性乳腺癌完全持久的消退。

使用检查点封锁或抗肿瘤淋巴细胞的过继转移进行的免疫疗法已显示出可有效治疗具有高体细胞突变水平的癌症（例如黑素瘤，吸烟引起的肺癌和膀胱癌），而对其他具有较低突变的常见上皮癌几乎没有作用率，例如在胃肠道，乳房和卵巢中产生的那些^1-7。特异性靶向由体细胞突变基因编码的蛋白质的自体淋巴细胞的过继转移已在转移性胆管癌，结肠癌和宫颈癌患者中介导了实质性客观的临床消退^8-11。我们介绍了一个化学难治性激素受体（HR）阳性转移性乳腺癌患者，该患者接受了对四种蛋白质-SLC3A2，KIAA0368，CADPS2和CTSB突变型有反应性的肿瘤浸润淋巴细胞（TILs）治疗。这些突变蛋白特异性TIL与白介素（IL）-2和检查点封锁的过继转移介导了转移性乳腺癌的完全持久消退，这种转移持续了22个月以上，它代表了一种新的免疫治疗方法。这些患者的治疗。