Photosensitizer-Antibody Conjugates (PhotoBodies): Emerging Frontiers in the Field of Theranostics

The beginning of precision medicine has come to rise in a new era of targeted therapies. Among these innovations, light-activatable antibody photo drug conjugates/photoimmunoconjugates termed as "PhotoBodies" have emerged as next-generation theranostic agents. By remaining inert until irradiated with a specific wavelength, PhotoBodies offer controlled diagnosis or treatment of diseased cells, tissues, or organs.

This review aims to summarize the evolution of new generation of photosensitizers, linkers, and antibody formats employed in PhotoBodies, to assess current preclinical and clinical developments, to identify unaddressed challenges, and propose a roadmap for future PhotoBodies.

We conducted a comprehensive literature survey focusing on studies reporting the designing and theranostic applications of PhotoBodies in both preclinical models and clinical trials.

More than 15 PhotoBodies are currently in clinical trials for targeted diagnosis and two for therapeutic application in cancers. PhotoBodies have also demonstrated their flexibility to combat the silent pandemic of the world i.e., non-oncological. Advances in photosensitizer chemistry have improved photostability, singlet-oxygen quantum yield, and tissue penetration. From conventional antibodies (full length antibodies/mAb) to non-conventional antibodies (antibody fragments including Fab, F(ab')₂, scFv, diabodies, minibodies, and single-domain antibodies), all the formats have been explored to balance the pharmacokinetics of PhotoBodies with tissue accessibility. PolyBodies^® based antibody partners in PhotoBodies have begun to enhance the clinical utility of PhotoBodies by improving their targeting efficacy. However, promising future includes key hurdles such as optimizing light delivery in deep tissues, managing immunogenicity, standardizing conjugation protocols, and navigating regulatory pathways.

PhotoBodies represent a promising frontier in precision theranostics by combining the specificity of antibody targeting with the controllability of photochemistry. Continued refinement of photosensitizer, linkers and antibody engineering will accelerate the clinical translation of PhotoBodies and realize their full potential in next-generation precision medicine. PolyBodies (containing polyvalent and polyspecific) based antibody carriers possess an upper hand in changing the current landscape of PhotoBodies and redefine their future.