POTENTIATING BREAST CANCER THERAPIES BY TARGETING TUMOR-ASSOCIATED MACROPHAGE

目前乳腺癌的治疗方法主要集中在杀死恶性细胞，但 这些方法最终失败的大量患者。长期 这项工作的目的是开发一种针对肿瘤促进基质的辅助治疗方法， 作为一种加强现有方法的方法。肿瘤相关巨噬细胞（TAM） 在肿瘤微环境中被激活，并通过促进 血管生成和肿瘤细胞生长，以及通过抑制适应性免疫应答。我们 最近鉴定了一种优先识别小鼠肿瘤相关的 巨噬细胞，而不是静息巨噬细胞、其他白细胞或肿瘤细胞。在这项工作中，我们将 制备多价靶向构建体以将促凋亡剂递送至小鼠中的TAM 乳腺癌模型。此外，我们还将开发类似的靶向肽， TAM。这些技术将结合在一个新的结构中，用于人体靶向消融。 TAM。我们的目标是将这项技术推向临床开发，并提供一个 辅助治疗是有效的，甚至对妇女的乳房无反应或三重 阴性乳腺癌。

Current treatments for breast cancer focus on the killing malignant cells but there is a substantial population of patients for whom these approaches ultimately fail. The long-term objective of this work is to develop an adjuvant therapy that targets the tumor-promoting stroma of cancer as a way to potentiate current approaches. Tumor-associated macrophages (TAMs) are activated in the tumor microenvironment and facilitate disease progression by promoting angiogenesis and tumor cell growth, and by suppressing the adaptive immune response. We have recently identified a peptide that preferentially recognizes murine tumor-associated macrophage but not resting macrophage, other leukocytes, or tumor cells. In this work, we will prepare multivalent targeting constructs to deliver pro-apoptotic agents to TAMs in a mouse model of mammary cancer. In addition, we will develop analogous targeting peptides for human TAMs. These technologies will be combined in a new construct for targeted ablation of human TAMs. Our goal is to move this technology toward clinical development and to provide an adjuvant treatment that is effective even for women with hormone-unresponsive or triple negative breast cancer.