Near-Infrared Photoimmunotherapy for Treatment of Colorectal Cancer in Orthotopic Nude-Mouse Models

<b>Background:</b> Photoimmunotherapy (PIT) employs the use of near-infrared (NIR) laser to activate an antibody conjugated to a NIR-activatable dye to promote cancer cell death. PIT has shown to be effective in a number of studies, however, there is no data on its use in colorectal cancers.<b>Methods:</b> Humanized anti-CEA antibody (M5A) was conjugated to NIR-activatable IRDye700DX (M5A-700). PIT was validated in vitro with a colon cancer cell line, using a laser intensity of either 4 J/cm², 8 J/cm², or 16 J/cm². Orthotopic colon cancer mouse-models were established by surgical implantation of LS174T tumor fragments onto the cecum. M5A-700 was administered and PIT was performed 24 hours later using a 690 nm laser. Repeat PIT was performed after 7 days in one group. Control mice received laser treatment only.<b>Results:</b> In vitro PIT demonstrated tumor cell death in a laser intensity dose-dependent fashion. In orthotopic models, control mice demonstrated persistent tumor growth. Mice that underwent PIT one time had tumor growth arrested for one week. The group that received repeated PIT exposure had persistent inhibition of tumor growth.<b>Conclusion:</b> PIT arrests tumor growth in colon cancer orthotopic nude-mouse models. Repeated PIT arrests colon cancer growth for a longer period of time. PIT may be a useful therapy in the future as an adjunct to surgical resection or as primary therapy to suppress tumor progression.<br>This data represents raw tumor volume in each mouse and average tumor volumes per group.