Therapeutic potential of photoimmunotherapy in solid tumors expressing CD98 heavy chain

Abstract

Abstract Near-infrared photoimmunotherapy (NIR-PIT) is an emerging targeted cancer therapy that uses an antibody–photoabsorber conjugate. In this study, we evaluated the therapeutic potential of NIR-PIT targeting CD98 heavy chain (CD98hc), a transmembrane glycoprotein that is highly expressed in various solid tumors and is associated with poor prognosis. We prepared a conjugate of the clinically tested anti-CD98hc antibody IGN523 and photoabsorber IRDye700DX (IGN523-IR700). The therapeutic efficacy was assessed in vitro using four CD98hc-expressing cancer cell lines and in an in vivo tumor xenograft mouse model. In vitro, IGN523-IR700 binds to cancer cells and induces rapid and light dose-dependent cell death upon near-infrared light exposure. In the in vivo model, intravenous administration of IGN523-IR700 followed by tumor-directed light irradiation resulted in significant tumor growth inhibition compared with that in the control groups. These results demonstrate that CD98hc is a viable and effective target for NIR-PIT. Given its widespread expression, targeting CD98hc may significantly broaden the applicability of NIR-PIT to diverse cancer types.