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Updated: Mar 19, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Phototheranostics of CD44-positive cell populations in triple negative breast cancer
Jiefu Jin1, Balaji Krishnamachary1, Yelena Mironchik1
1Division of Cancer Imaging Research, The Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
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 CD44(high)/CD24(low), 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.
Insights
A new CD44-targeted therapy shows promise for treating triple-negative breast cancer (TNBC). This approach uses a photosensitizer conjugate to eliminate cancer stem-like cells, offering a potential new treatment for advanced and metastatic TNBC.
Area of Science:
- Oncology
- Biotechnology
- Immunotherapy
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options.
- Cancer stem-like cells (CSCs) contribute to TNBC recurrence and metastasis due to therapy resistance.
- CD44(high)/CD24(low) phenotype, ABCG2 transporter, and ALDH1 expression are associated with CSCs.
Purpose of the Study:
- To develop a CD44-targeted photosensitizer conjugate for fluorescent detection and photoimmunotherapy (PIT) of TNBC.
- To evaluate the efficacy of this conjugate in eliminating CD44-expressing cells, including CSCs, in TNBC models.
Main Methods:
- Development of a monoclonal antibody-photosensitizer conjugate targeting CD44.
- In vitro assessment of conjugate-mediated cell killing in CD44-expressing breast cancer cells.
- In vivo evaluation of conjugate accumulation, tumor shrinkage, and CSC elimination in CD44-positive TNBC tumors following near-infrared irradiation.
Main Results:
- The CD44-targeted conjugate demonstrated potent, CD44-dependent cell killing of breast cancer cells.
- Near-infrared irradiation in combination with the conjugate led to selective tumor accumulation and significant tumor shrinkage.
- Efficient elimination of CD44-positive cell populations, including CSCs, was observed post-irradiation.
Conclusions:
- The novel CD44-targeted phototheranostic strategy effectively destroys CD44-positive cells, including CSCs, in TNBC.
- This approach offers a promising new avenue for treating locally advanced primary and metastatic TNBC.
- The developed conjugate facilitates both fluorescent detection and targeted photoimmunotherapy for TNBC.
