Radioimmunotherapy: Mechanisms, Strategies, and Advances in Therapeutic Enhancement.

Abstract

Radioimmunotherapy (RIT) represents a paradigm shift in precision cancer therapy by integrating the molecular specificity of monoclonal antibodies with the cytotoxic potential of therapeutic radionuclides. However, the therapeutic success of RIT is not merely associated with targeted radiation delivery but also depends on complex interplay of radiobiology, tumor immunology, antibody pharmacology, and patient-specific dosimetry. This review explores the molecular and cellular mechanisms, including DNA damage response, immunogenic cell death, tumor microenvironment remodeling, cytokine signaling, and bystander/abscopal effects of RIT. The role of key pharmacological determinants such as target antigen selection, antibody engineering, radionuclide chemistry, radiolabeling strategies, pharmacokinetics, biodistribution, and personalized dosimetry will also be evaluated for therapeutic effectiveness of RIT. Furthermore, translational challenges such as heterogeneous antigen expression, limited tumor penetration, dosimetric uncertainty, and immune-mediated therapeutic resistance in addition to logistical barriers have also been discussed.