IMMUNOTHERAPY OF EARLY, LATE, AND DORMANT METASTASES

描述（改编自申请人的摘要）：该项目是 基于NK细胞在体内或体外激活的假设， 体内（并随后转移回受体），可能 构成了扩散性癌症的有效疗法。申请人 因此，将测试和比较活化的抗肿瘤作用， 不同时期大鼠播散性乳腺癌模型中NK细胞的变化 的进展（即，早期、晚期和休眠转移）。这将 通过以下方式完成：1）测量两种内源性NK细胞的积累 并将IL-2激活的NK细胞（A-NK）过继转移到早期和晚期， 晚期MADB 106乳腺癌转移，以及NK细胞 攻击和破坏这种病变; 2）确定的能力， 内源性NK细胞和过继转移的A-NK细胞定位 EMS-86乳腺癌的休眠与活动转移， 以及分析内源性NK细胞的激活和/或 在转移性肿瘤的休眠状态期间A-NK细胞的过继转移 乳腺癌疾病可以防止转移性生长的复发。 此外，还将进行研究，以评价粘附性和 参与内源性NK细胞定位的分子， 将A-NK细胞转移到转移瘤中， NK/A-NK细胞介导的抗肿瘤作用。研究者 相信这些研究将提供信息和见解， 可能会转化为新的临床策略， 转移性乳腺癌的女性，并确定大小和/或 最可能对免疫应答的转移阶段 基于NK细胞的方法。

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.