The feasibility of Miltuximab®-IRDye700DX-mediated photoimmunotherapy of solid tumors

摘要

Background: Photoimmunotherapy (PIT) is an emerging method of cancer treatment based on the use of a photosensitizer near-infrared dye IRDye700DX (IR700) conjugated to a monoclonal antibody. The antibody selectively delivers IR700 to cancer cells, which can then be killed after photoexcitation. Glypican-1 (GPC-1) is a novel target expressed specifically in malignant tumors. We aimed to investigate whether anti-GPC-1 antibody Miltuximab (R) (Glytherix Ltd., Sydney, Australia) can be conjugated with IR700 for PIT of solid tumors.Methods: The dye IR700 was conjugated with Miltuximab (R) and characterized by spectrophotometry and flow cytometry. Miltuximab (R)-IR700-mediated PIT was tested in prostate (DU-145), bladder (C3 and T-24), brain (U87 and U-251) and ovarian (SKOV-3) cancer cell lines. After 1 h incubation with Miltuximab (R)-IR700, the cells were washed by PBS and illuminated using a 690-nm light-emitting diode. The viability of the cells was assessed by a CCK-8 viability kit 24 h later.Results: Miltuximab (R)-IR700-mediated PIT caused 67.3-92.3% reduction in viability of cells with medium-high GPC-1 expression and did not affect the viability of GPC-1-low cells. Cytotoxicity was attributed to the targeted binding of the conjugate with subsequent photoactivation, as the conjugate or light exposure alone had no effect on the cell viability. Miltuximab (R)-IR700 did not induce cytotoxicity in cells blocked by unconjugated Miltuximab (R).Conclusions: PIT with Miltuximab (R)-IR700 appears to be highly specific and effective against GPC-1-expressing cancer cells, indicating that it holds promise for an effective and safe treatment of early stage solid tumors or as adjuvant therapy following surgical resection. These findings necessitate further investigation of PIT with Miltuximab (R)-IR700 in other GPC-1-expressing cancer cell lines in vitro and in vivo in xenograft tumor models.