Photoimmunotherapy Targeting Prostate-Specific Membrane Antigen: Are Antibody Fragments as Effective as Antibodies?

Photoimmunotherapy is a highly cell-selective cancer therapy based on an armed antibody conjugate with a phthalocyanine-based photosensitizer, IR700. Photoimmunotherapy induces rapid and highly specific necrosis in targeted cancer cells after exposure to near-infrared (NIR) light. Cells not expressing the antigen are not affected. To date, photoimmunotherapy has been demonstrated only with full antibody-IR700 conjugates. In this study, small and bivalent antibody fragments, including anti–prostate-specific mem-brane antigen (PSMA) diabody (Db) and minibody (Mb), were com-pared with intact IgG for their effectiveness as photoimmunotherapy agents.Methods: Radioiodinated antibody and antibody fragments with 125I were used to determine the timing of maximum binding of each anti-PSMA antibody fragment on the cell surface in vivo in mice bearing either PSMA-positive or-negative PC3 tumors. Then therapeutic efficacy of photoimmunotherapy was examined by ex