IMMUNOTHERAPY OF EARLY, LATE, AND DORMANT METASTASES

描述(改编自申请者摘要)：本项目为 基于NK细胞在体内或外部被激活的假设 体内(并随后转移回接收者)，可能 构成了治疗播散性癌症的有效方法。申请人 因此将测试和比较激活的抗肿瘤效果 不同阶段播散性乳腺癌大鼠模型中NK细胞的表达 进展(即早期、晚期和潜伏性转移)。这将是 通过：1)测量两种内源性NK细胞的积累量 并过继将IL-2激活的NK(A-NK)细胞转移到早期和 晚期乳腺癌MADB106转移与NK细胞范围的关系 攻击和破坏这种损害；2)确定 内源性NK细胞和过继转移的A-NK细胞的定位 EMS-86乳腺癌的隐匿性转移与活动性转移的比较， 并分析内源性NK细胞的激活和/或 A-NK细胞在转移休眠状态下的过继转移 乳腺癌疾病可以防止复发的转移生长。 此外，还将进行研究，以评估这两种附着力 参与内源性NK细胞定位和过继免疫的分子 转移的A-NK细胞转移及其机制的研究 NK/A-NK细胞介导的抗肿瘤作用调查员 相信这些研究将提供信息和见解， 可能会转化为改进治疗的新临床策略 并确定转移性乳腺癌的大小和/或 最有可能对免疫治疗有反应的转移阶段 以NK细胞为基础的治疗方法。

DESCRIPTION (Adapted from the Applicant's Abstract): This project is based on the hypothesis that NK cells, activated either in vivo or ex vivo (and subsequently transferred back into the recipient), might constitute an effective therapy of disseminated cancer. The applicant will therefore test and compare the anti-neoplastic effect of activated NK cells in rat models of disseminated breast cancer at different stages of progression (i.e., early, late, and dormant metastases). This will be done by: 1) measuring the accumulation of both endogenous NK cells and adoptively transferred IL-2-activated NK (A-NK) cells into early and late MADB106 mammary carcinoma metastases, and the extent of NK cell attack and destruction of such lesions; 2) determining the ability of endogenous NK cells and adoptively transferred A-NK cells to localize into dormant versus active metastases of the EMS-86 mammary carcinoma, and analyzing whether activation of endogenous NK cells and/or the adoptive transfer of A-NK cells during the dormant state of metastatic breast cancer disease can prevent the recurrence of metastatic growth. Furthermore, studies will be carried out to evaluate both the adhesion molecules involved in localization of endogenous NK cells and adoptively transferred A-NK cells into metastases and the mechanisms behind the anti-neoplastic effects mediated by NK/A-NK cells. The investigator believes that these studies will provide information and insights that might be translatable to new clinical strategies for improving treatment of women with metastatic breast cancer and identify the size and/or stage of metastases most likely to respond to immunotherapeutic approaches based on NK cells.