Development of anti-CCR4 scFv-photoabsorber Conjugate for Enhanced Near-infrared Photoimmunotherapy Targeting Adult T-cell Leukemia Cells

Near-infrared photoimmunotherapy (NIR-PIT) is an emerging, highly-selective, cancer-therapeutic modality that combines molecular targeting with photochemistry. The mechanism of NIR-PIT involves conjugating antibodies with the photosensitizer IRDye700DX (IR700), which is activated by NIR light to induce localized cell death. This approach offers several advantages, including minimal off-target effects, rapid immunogenic cell death, and precise tumor-antigen targeting. Conventional full-length antibodies are effective in many therapeutic applications; however, their Fc regions can trigger unintended immune responses and effector-function-mediated toxicity, thereby reducing safety and efficacy of antibody-based therapies. To overcome these challenges, we investigated the feasibility of using a mogamulizumab-derived, single-chain variable fragment (Moga-scFv) targeting CC chemokine receptor 4 (CCR4), a common marker in adult T-cell leukemia/lymphoma (ATL). The Moga-scFv–IR700 conjugate was successfully prepared and efficiently killed CCR4-positive cells upon NIR irradiation at levels similar to Moga-IgG. This study demonstrates the potential of Moga-scFv–IR700 in NIR-PIT for ATL treatment, supporting the feasibility of scFvs as alternative antibody format.