Phototheranostics of CD44-positive cell populations in triple negative breast cancer

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....

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Bibliographic Details
Published in:Scientific reports 2016-06, Vol.6 (1), p.27871-27871, Article 27871
Main Authors: Jin, Jiefu, Krishnamachary, Balaji, Mironchik, Yelena, Kobayashi, Hisataka, Bhujwalla, Zaver M.
Format: Article
Language:English
Subjects:
13/2
13/31
13/51
14/19
64/60
692/4017
692/4028/67/1059/602
692/4028/67/1347
692/4028/67/71
Animals
Antibodies, Monoclonal - chemistry
Antibodies, Monoclonal - immunology
Breast cancer
Cell Death - drug effects
Cell Line, Tumor
Female
Humanities and Social Sciences
Humans
Hyaluronan Receptors - immunology
Hyaluronan Receptors - metabolism
Immunoconjugates - chemistry
Immunoconjugates - metabolism
Immunoconjugates - pharmacology
Immunotherapy - methods
Irradiation
Mice, Inbred BALB C
Molecular Targeted Therapy - methods
multidisciplinary
Photosensitizing Agents - pharmacology
Phototherapy - methods
Science
Tissue Distribution
Triple Negative Breast Neoplasms - therapy
Xenograft Model Antitumor Assays
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep27871