Visonneau S, Cesano A, Torosian M H, Santoli D
The Wistar Institute, and The Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Clin Cancer Res. 1997 Sep;3(9):1491-500.
Although enormous progress has been made in the detection and treatment of localized (nonmetastatic) breast cancer, there has been relatively moderate progress toward the effective treatment of advanced disease. This study investigates the antitumor efficacy of a potent MHC nonrestricted cytotoxic human T cell line (TALL-104) upon transfer into a clinically relevant mouse model of metastatic breast cancer. Fragments from a surgical specimen of a patient with infiltrating ductal carcinoma were implanted s.c. in the flank region of severe combined immunodeficient (SCID) mice. One hundred % of the animals developed a local tumor mass that metastasized to subaxillary and inguinal lymph nodes, bones, lungs, liver, kidneys, ovaries, and brain, very closely mimicking the human disease. Multiple i.p. transfers of gamma-irradiated (nonproliferating) TALL-104 cells into mice bearing low tumor burden (the primary tumor mass weighed only 150 mg) completely arrested local tumor growth and prevented systemic spread into local lymph nodes and distant organs. Remarkably, cell therapy administered in an advanced disease stage (when the tumor weighed 2 g) induced a significant or total regression of established metastasis with no obvious effects on the primary tumor mass. Profound antitumor effects against both local and systemic disease were instead seen in mice that received cell therapy after surgical excision of the primary tumor. The implications of these data in adjuvant breast cancer therapy are discussed.
尽管在局部（非转移性）乳腺癌的检测和治疗方面已经取得了巨大进展，但在晚期疾病的有效治疗方面进展相对有限。本研究调查了一种强效的主要组织相容性复合体（MHC）非限制性细胞毒性人T细胞系（TALL-104）在转入具有临床相关性的转移性乳腺癌小鼠模型后的抗肿瘤疗效。将一名浸润性导管癌患者手术标本的片段皮下植入严重联合免疫缺陷（SCID）小鼠的胁腹区域。100%的动物形成了局部肿瘤块，并转移至腋下和腹股沟淋巴结、骨骼、肺、肝、肾、卵巢和脑，非常接近人类疾病的情况。将经γ射线照射（不增殖）的TALL-104细胞多次腹腔内注射到肿瘤负荷低的小鼠（原发肿瘤块仅重150毫克）中，完全阻止了局部肿瘤生长，并防止了全身扩散至局部淋巴结和远处器官。值得注意的是，在疾病晚期（肿瘤重2克时）进行细胞治疗可使已形成的转移灶显著或完全消退，而对原发肿瘤块无明显影响。相反，在原发肿瘤手术切除后接受细胞治疗的小鼠中，观察到对局部和全身疾病均有显著的抗肿瘤作用。讨论了这些数据在辅助性乳腺癌治疗中的意义。
