Recent years have seen a noteworthy increase in ADC therapy clinical trials, marked by the initiation of numerous new therapies in 2022

Recent years have seen a noteworthy increase in ADC therapy clinical trials, marked by the initiation of numerous new therapies in 2022. York, NY, USA), AbbVie Pharmaceuticals Inc. (USA), Regeneron Pharmaceuticals Inc. (Tarrytown, NY, USA), and Seagen Inc. (Bothell, WA, USA). While ADC therapy holds great promise in anticancer treatment, challenges persist, including premature payload release and immune-related side effects. Ongoing research and development are crucial for advancing ADC therapy. Future developments may include novel conjugation methods, stable linker designs, efficient payload delivery technologies, and integration with nanotechnology, driving the evolution of ADC therapy in anticancer treatment. Keywords:antibodydrug conjugates (ADCs), technology trends, intellectual property (IP) landscape, market, key players, innovation == 1. Background of ADC Therapeutic Technology == The antibodydrug conjugate (ADC) therapy technology is a next-generation therapeutic approach to overcome the limitations of conventional cancer chemotherapy. It is considered one of the next-generation anticancer treatment technologies that leverage the targeted selectivity of antibodies and the cell-killing efficacy of cytotoxic drugs to enhance therapeutic effects while minimizing side effects [1,2,3,4]. This technology involves the use of a drug composed of a low-molecular-weight cytotoxic agent (chemotherapeutic drug) chemically linked to an antibody that interacts with a specific antigen overexpressed on the surface of cancer cells through a chemical linker (Figure 1). Toxoflavin This structure allows for the targeted delivery of the cytotoxic drug to cancer cells, enhancing the effectiveness of the anticancer treatment while minimizing adverse effects. == Figure 1. == Characteristics and structure of ADC [1]. Copyright 2022 Springer Nature. The optimal ADC therapy is characterized Toxoflavin by its ability to maintain stability in the bloodstream, accurately reach targeted cancer cells, IL1F2 and ultimately release the cytotoxic payload in close proximity to the specified cancer cells for effective treatment. Essential components of ADCs in achieving these objectives encompass tumor-targeting antibodies designed to correspond to antigens expressed on cancer cells, along with linkers and cytotoxic payloads. The conjugation methods employed for these components represent a critical technological aspect in ADC manufacturing, enabling the precise assembly of these elements and ensuring optimal therapeutic outcomes. == 1.1. Selection of Target Antigens == The target antigen expressed on cancer cells serves as the navigation system for ADC therapy, determining the mechanism for recognizing cancer cells and delivering the cytotoxic payload. The selection of an ideal target antigen is the first crucial consideration in this process. The criteria for the ideal selection of a target antigen typically involve its overexpression in cancer cells while being rare or very lowly expressed in normal tissues. Additionally, the antigen should be expressed on the surface of cancer cells. It is also essential that the chosen antigen is not secreted in the bloodstream to avoid unwanted binding of ADCs in undesired locations. Currently developed ADC therapies have selected target antigens such as HER2, trop2, nectin4, and EGFR for solid tumors and CD19, CD22, CD33, CD30, BCMA, and CD79b for hematologic malignancies [1,5,6]. These antigens have been chosen based on their overexpression in cancer cells and their suitability for effective ADC therapy. == 1.2. Cancer Cell-Targeting Antibodies Toxoflavin == Antibodies targeting cancer cells play a pivotal role in facilitating specific binding between the target antigen and ADCs. These antibodies should demonstrate high binding affinity to the target antigen, low immunogenicity, and an extended half-life. In the initial stages of ADC therapy development, antibodies derived from mice were commonly utilized. However, due to severe immunogenic side effects, especially associated with murine antibodies, the prevailing trend now predominantly favors the use of humanized antibodies produced through recombinant technology [7,8,9]. Humanized antibodies are generated by incorporating key regions of the mouse-derived antibody into a human antibody framework. This approach preserves the specificity Toxoflavin and high binding affinity of the mouse antibody while minimizing the risk of immune reactions in humans. The transition towards humanized antibodies has Toxoflavin significantly contributed to enhancing the safety and efficacy of ADC therapies. == 1.3. Linkers == The linker in ADCs plays a crucial role in bridging the antibody and the cytotoxic drug, representing a critical determinant of ADC stability and the profile of payload drug release. This, in turn, significantly influences therapeutic efficacy. An ideal linker should avoid inducing ADC aggregation, prevent premature payload release in the bloodstream, and facilitate the release of active drugs precisely at the desired target. Linkers are broadly classified into two main types based on cellular metabolism processes [10,11,12,13]: cleavable linkers and.