POTENTIATING BREAST CANCER THERAPIES BY TARGETING TUMOR-ASSOCIATED MACROPHAGE

描述（由申请人提供）：目前乳腺癌的治疗重点是杀死恶性细胞，但有相当数量的患者，这些方法最终失败。这项工作的长期目标是开发一种靶向肿瘤促进基质的辅助治疗方法，作为增强现有方法的一种方法。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抑制适应性免疫反应来促进疾病进展。我们最近发现了一种肽，它优先识别小鼠肿瘤相关的巨噬细胞，而不是静止的巨噬细胞，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物，将促凋亡药物输送到乳腺癌小鼠模型中的tam中。此外，我们将开发类似的针对人类tam的靶向肽。这些技术将结合在一个新的结构中，用于人类tam的靶向消融。我们的目标是将这项技术推向临床发展，并提供一种辅助治疗，即使对激素无反应或三阴性乳腺癌的女性也有效。

DESCRIPTION (provided by applicant): 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.