EpCAM-targeted near-infrared photoimmunotherapy (NIR-PIT) for the treatment of breast cancer.

BACKGROUND

Near-infrared photoimmunotherapy (NIR-PIT) is a targeted cancer treatment that uses antibody-IR700 conjugates and selectively destroys cancer cells expressing a target antigen when exposed to near-infrared (NIR) light. NIR-PIT not only destroys targeted cancer cells but also induces anticancer immune activation. Currently, epidermal growth factor receptor (EGFR) is the only clinically approved target for NIR-PIT. To expand the therapeutic potential of this therapy, we investigated EpCAM as a potential target for NIR-PIT.

METHOD: We first evaluated the target cell-killing efficacy of EpCAM-targeted NIR-PIT (EpCAM-NIR-PIT) using the antibody Edrecolomab in human breast and colon cancer models characterized by high EpCAM expression. Next, we evaluated anticancer immune activity induced by EpCAM-NIR-PIT with an anti-PD-1 immune checkpoint inhibitor in a mouse breast cancer model in immunocompetent mice.

RESULT: Both in vitro and in vivo studies demonstrated effective cell killing in response to EpCAM-NIR-PIT using Edrecolomab. In vivo EpCAM-NIR-PIT in a breast cancer model in immunodeficient mice demonstrated an initial reduction in tumour size followed by delayed regrowth relative to controls. The analysis of immune cells revealed that this combination therapy led to robust activation of CD8+ T cells and their differentiation into effector cells, resulting in significant tumour suppression with a 50% complete remission (CR) rate. Furthermore, mice that achieved CR demonstrated resistance to tumour rechallenge, indicating the establishment of long-term anticancer immunity.

CONCLUSION

This study demonstrated that EpCAM-NIR-PIT, particularly when combined with immune-activating agents such as anti-PD-1, is a promising new approach for cancer treatment, inducing durable and systemic anticancer immunity.