Targeted protein degradation or TPD, is rapidly emerging as a treatment that utilizes small molecules to degrade proteins that cause diseases. TPD allows for the selective removal of disease-causing proteins, including proteasome-mediated degradation, lysosome-mediated degradation, and autophagy-mediated degradation. This approach has shown great promise in preclinical studies and is now being translated to treat numerous diseases, including neurodegenerative diseases, infectious diseases, and cancer. This review discusses the latest advances in TPD and its potential as a new chemical modality for immunotherapy, with a special focus on the innovative applications and cutting-edge research of PROTACs (Proteolysis TArgeting Chimeras) and their efficient translation from scientific discovery to technological achievements. Our review also addresses the significant obstacles and potential prospects in this domain, while also offering insights into the future of TPD for immunotherapeutic applications.

Department of Biotechnology Heritage Institute of Technology Kolkata 700107 India

Department of Biotechnology Indian Institute of Technology Madras Chennai 600036 India

Department of Chemical Pathology School of Pathology Faculty of Health Sciences University of the Free State Bloemfontein Free State 9300 South Africa

Department of Chemistry School of Physical Sciences Central University of Kerala Tejaswini Hills Periye Kasaragod District Kerala 671320 India

Department of Pharmacology and Toxicology Faculty of Pharmacy Charles University Prague Heyrovskeho 1203 50005 Hradec Kralove Czech Republic

Discipline of Medical Biochemistry School of Laboratory Medicine and Medical Sciences College of Health Sciences Howard College Campus University of KwaZulu Natal Durban 4041 South Africa

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