Engineering Bispecific Nanobodies for Detection of Breast Cancer Nodal Metastasis
Abstract
Axillary lymph node status, i.e., the presence or absence of metastasis in the lymph nodes closest to the tumor, is a key determinant of prognosis and is used to determine the path of treatment of breast cancer. Pre-operative lymph node mapping for sentinel lymph node identification and surgical biopsy for standard histologic analysis remains the current gold standard for the evaluation of axillary lymph nodes in breast cancer where metastasis is determined by pathology after removal of the nodes. However, surgical biopsy of sentinel lymph nodes is invasive, morbid, and expensive, and 64% of breast cancer patients who undergo sentinel lymph node biopsy are determined to be pathologically negative. Numerous un-targeted agents have been used to map or identify sentinel lymph nodes such as sulfur colloids, blue dyes, and nanomaterials, which collect non-selectively into the draining lymph nodes with only transient and non-specific visualization of the lymphatic system. We propose to address the overarching challenges of conquering a problem of overtreatment and revolutionizing a standard surgical practice by replacing it with a more effective approach with decreased morbid side effects. The goal of this proposal is to develop and test new breast cancer targeted imaging agents for the non-invasive (non-surgical) detection of breast cancer lymph node metastases and surgical removal of only the nodes with metastases when detected. This has potential to eliminate the need for the standard surgical biopsy and dissection of all regional lymph nodes, which are highly invasive procedures, cause significant morbidities, and are expensive. Furthermore, most patients who undergo lymph node surgical biopsy are pathologically negative. Identification of breast cancer lymph node metastasis without surgical exploration will revolutionize the entire practice of breast cancer surgery, eliminating the need for surgical biopsy while reducing the morbidity of lymph node dissection for patients with known metastases. This capability will positively affect the treatment of 85% of all operable breast cancers, approximately 245,000 American women a year. By the end of the three year study, we will have identified lead targeted imaging agents that can be further refined and undergo U.S. Federal Drug Administration Investigational New Drug enabling studies and first-in-human clinical trials.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210080
Entities
People
- David Morse
Organizations
- H. Lee Moffitt Cancer Center & Research Institute
- United States Army