![]() ![]() There are 328 unique antigens used in antibody-based therapy as a target ( 11). ![]() One of the most important aspects of ADC development for cancer is the identification of the unique antigenic target of the mAb component. ADCs empower selective delivery of highly potent drugs to tumor cells while sparing healthy cells, attenuating the main clinical obstacle of traditional chemotherapy, thus providing a broad therapeutic window. This technology consists of highly specific mAbs attached to extremely cytotoxic agents with the help of various linkers. The first ADCs based on chimeric and humanized mAbs were testified in the 1990s ( 10). In the 1980s, clinical trials of ADCs grounded on mouse IgG molecules were performed. Forty-five years later, in accordance with the concept of Paul Ehrlich, methotrexate was attached to an antibody against leukemia cells ( 9). Ehrlich also anticipates attaching toxin to the antibodies to improve their therapeutic specificity. He described the antibody as a “magic bullet” that identifies their target themselves without harming the organism ( 8). The concept of ADC was first presented by the German physician and scientist Paul Ehrlich almost 100 years before. Despite advances in anticancer chemotherapy, the use of small-molecule anticancer drugs as the most widely used chemotherapeutic drugs ( 5), has withstood enormous hurdles demonstrating limited selectivity against cancer cells, systemic toxicity, and drug resistance development that results in the narrow therapeutic window, and thus limiting its efficacy ( 6).Īntibody–drug conjugate (ADC) is a new emerging class of highly potent pharmaceutical drugs, which is a great combination of chemotherapy and immunotherapy. Thereafter, antifolates such as methotrexate, DNA synthesis inhibitors like thioguanine, 5-fluorouracil, and cytosine arabinoside (ara-C), and DNA interacting agents like cisplatin, actinomycin D, anthracyclines, and Vinca alkaloids entered the foray of drugs used for the treatment of cancer. This chemotherapeutic agent exerts its cellular apoptotic action by DNA alkylation. ![]() On the basis of this concept, nitrogen mustard was tested in humans resulting in the eradication of bone marrow and lymphoid tissues in patients suffering from cancer ( 4). This concept is based on the premise that these agents would not harm normal cells while preferentially kill rapidly dividing tumor cells. Among these treatment options, chemotherapy was the principal therapeutic intervention for treating cancer ( 2, 3). The therapeutic interventions used for treating can/tumor include chemotherapy, immunotherapy, radiation, stem cell therapy, laser treatment, hyperthermia, surgery, photodynamic therapy, etc. Moreover, this review also shed light on the current status of ADCs that have gained regulatory approval from the FDA including a description of biology and chemistry, metabolic profiles, adverse events, drug interactions, and the future perspective on combination strategies with other agents, including immunotherapy.Ĭancer is the second most common fatal disease, causing approximately 8.2 million deaths worldwide each year ( 1). This review provides an overview of the systemic evaluation of each component of an ADC design, improved understanding of the mechanism of action of ADC, and mechanistic pathways involved in ADC resistance and various strategies to optimize ADC design. Selection of an appropriate target, an mAb, cytotoxic payload, and the manner in which the antibody is linked to the payload are key determinants of the safety and efficacy of ADCs. ADCs are complex molecules that require careful attention to various components. This approach comprises a mAb conjugated to the cytotoxic payload via a chemical linker that directed toward a target antigen expressed on the cancer cell surface, reducing systemic exposure and therefore toxicity. Antibody–drug conjugates (ADC) are one of the fastest growing anticancer drugs. ![]()
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