Highly versatile cancer photoimmunotherapy using photosensitizer-conjugated avidin and biotin-conjugated targeting antibodies

Autor: Hirotomo Shibaguchi, Naoto Shirasu, Hiromi Yamada, Masahide Kuroki, Shin'ichiro Yasunaga
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Cancer Cell International, Vol 19, Iss 1, Pp 1-13 (2019)
Cancer Cell International
ISSN: 1475-2867
Popis: Background Photoimmunotherapy (PIT) employing antibody-photosensitizer conjugates is a promising treatment for cancer. However, the fixed antigen specificity severely limits the efficacy and the applicability. Here we describe a universal strategy for PIT of cancer by using a near-infrared (NIR) photosensitizer IRDye700DX-conjugated NeutrAvidin, designated as AvIR, together with various biotinylated antibodies (BioAbs) for cellular targeting. Methods Cytotoxicity of AvIR-mediated PIT was evaluated by fluorescence imaging and cell viability assay. Phototoxic effect on tumorigenicity was assessed by tumorsphere-formation assay and Matrigel invasion assay. Cancer stem cell-like side-population (SP) cells were identified by flow cytometry. Results CHO cells stably expressing carcinoembryonic antigen or EpCAM were pre-labeled with each BioAb for the corresponding antigen, followed by AvIR administration. NIR light irradiation specifically killed the targeted cells, but not off-targets, demonstrating that the AvIR-mediated PIT does work as expected. CSC-like subpopulation of MCF-7 cells (CD24low/CD44high) and SP of HuH-7 cells (CD133+/EpCAM+) were effectively targeted and photokilled by AvIR-PIT with anti-CD44 BioAb or anti-CD133/anti-EpCAM BioAbs, respectively. As results, the neoplastic features of the cell lines were sufficiently suppressed. Cancer-associated fibroblast (CAF)-targeted AvIR-PIT by using anti-fibroblast activation protein BioAb showed an abolishment of CAF-enhanced clonogenicity of MCF-7 cells. Conclusions Collectively, our results demonstrate that AvIR-mediated PIT can greatly broaden the applicable range of target specificity, with feasibility of efficacious and integrative control of CSC and its microenvironment.
Databáze: OpenAIRE
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