Abstract
Photodynamic therapy (PDT) utilize a photosensitizing agent and light for cancer therapy. It exerts anti-cancer effect mainly by inducing vascular occlusion at the irradiated site. By controlling the irradiation area, PDT can be used in a tumor-specific manner. However, the non-specific cellular damage in the surrounding normal tissue is still a serious concern. Photoimmunotherapy (PIT) is a new type of targeted cancer therapy that uses an antibody-photon absorber conjugate (APC). The superiority of PIT to PDT is the improved target specificity, thereby reducing the damage to normal tissues. Here, we developed a novel APC targeting epithelial cell adhesion molecule (EpCAM) as well as a negative control APC that does not bind to the EpCAM antigen. Our in vitro analysis of APC cytotoxicity demonstrated that the EpCAM APC, but not the negative control, was cytotoxic to EpCAM expressing COLO 205 cells after photoirradiation, suggesting that the cytotoxicity is antigen-dependent. However, in our in vivo analysis using a mouse xenograft tumor model, decreased volume of the tumors was observed in all the mice treated with irradiation, regardless of whether they were treated with the EpCAM APC or the negative control. Detailed investigation of the mechanism of these in vivo reveal that both APCs induce vascular occlusion at the irradiation site. Furthermore, the level of vascular occlusion was correlated with the blood concentration of APC, not the tumor concentration. These results imply that, similar to PDT, PIT can also induce non-targeted vascular occlusion and further optimization is required before widespread clinical use.
Highlights
Various antibody drug conjugates (ADCs), which are formed by linking a cytotoxic drug to a monoclonal antibody, have been developed to enhance the tumor selectivity of anti-cancer payloads [1]
In our in vivo analysis using a mouse xenograft tumor model, decreased volume of the tumors was observed in all the mice treated with irradiation, regardless of whether they were treated with the epithelial cell adhesion molecule (EpCAM) APC or the negative control
It appears that the drug-to-antibody ratio (DAR) of EpCAM-IRDye700DX NHS ester (IR700) and DNP-IR700 were 2.16 and 2.05, respectively
Summary
Various antibody drug conjugates (ADCs), which are formed by linking a cytotoxic drug to a monoclonal antibody, have been developed to enhance the tumor selectivity of anti-cancer payloads [1]. Side-effects caused by the expression of antigen on normal tissue are detrimental and difficult to overcome using conventional ADC technology. Photodynamic therapy (PDT) utilizes a photosensitizing agent in association with the physical energy of non-ionizing light to exert cytotoxic effects via the induction of vascular occlusion at the irradiation site [5]. Because the photosensitizing agents currently in use are often not specific enough, some side-effects, such as normal tissue damage, have been observed [5]
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