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. 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.
Division of Cancer Imaging Research, The Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jiefu
J
Jin
Division of Cancer Imaging Research, The Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Balaji
B
Krishnamachary
Division of Cancer Imaging Research, The Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Yelena
Y
Mironchik
Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA.
Hisataka
H
Kobayashi
Division of Cancer Imaging Research, The Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Zaver M
ZM
Bhujwalla
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology* / Q000378:metabolism; D018796:Immunoconjugates / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D007167:Immunotherapy / Q000379:methods*; D008807:Mice, Inbred BALB C; D058990:Molecular Targeted Therapy / Q000379:methods; D017319:Photosensitizing Agents / Q000494:pharmacology; D010789:Phototherapy / Q000379:methods*; D014018:Tissue Distribution; D064726:Triple Negative Breast Neoplasms / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D018796:Immunoconjugates; D017319:Photosensitizing Agents