Abstract
Triple-negative breast cancer (TNBC) is one of the most lethal subtypes of breast cancer that has limited treatment options. Its high rates of recurrence and metastasis have been associated, in part, with a subpopulation of breast cancer stem-like cells that are resistant to conventional therapies. A compendium of markers such as CD44high/CD24low, and increased expression of the ABCG2 transporter and increased aldehyde dehydrogenase (ALDH1), have been associated with these cells. We developed a CD44-targeted monoclonal antibody photosensitizer conjugate for combined fluorescent detection and photoimmunotherapy (PIT) of CD44 expressing cells in TNBC. The CD44-targeted conjugate demonstrated acute cell killing of breast cancer cells with high CD44 expression. This cell death process was dependent upon CD44-specific cell membrane binding combined with near-infrared irradiation. The conjugate selectively accumulated in CD44-positive tumors and caused dramatic tumor shrinkage and efficient elimination of CD44-positive cell populations following irradiation. This novel phototheranostic strategy provides a promising opportunity for the destruction of CD44-positive populations that include cancer stem-like cells, in locally advanced primary and metastatic TNBC.
Highlights
Triple-negative breast cancer (TNBC) is one of the most lethal subtypes of breast cancer that has limited treatment options
Since endocrine and HER2-targeted therapies are ineffective in triple-negative breast cancer (TNBC), cytotoxic chemotherapy remains the mainstay of systemic treatment for TNBC patients[2,3]
After removing unbound IRDye 700DX NHS ester (IR700) moieties, we measured an average of three IR700 molecules conjugated to one CD44 monoclonal antibodies (mAbs) by UV spectroscopy
Summary
Triple-negative breast cancer (TNBC) is one of the most lethal subtypes of breast cancer that has limited treatment options. CD44-IR700-mediated PIT selectively kills CD44 expressing triple negative MDA-MB-231, SUM149 and SUM159 breast cancer cells.
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