In cancer treatment, the first-generation, cytotoxic drugs, though effective against cancer cells, also harmed healthy ones. The second-generation targeted cancer cells precisely to inhibit their growth. Enter the third-generation, consisting of immuno-oncology drugs, designed to combat drug resistance and bolster the immune system’s defenses. These advanced therapies operate by obstructing the uncontrolled growth and spread of cancer cells through the body, ultimately eliminating them effectively. Within the arsenal of cancer treatment, monoclonal antibodies offer several advantages, including inducing cancer cell apoptosis, precise targeting, prolonged presence in the body, and minimal side effects. A recent development in cancer therapy is Antibody-Drug Conjugates (ADCs), initially developed in the mid-20th century. The second generation of ADCs addressed this issue through innovative antibody modification techniques, such as DAR regulation, amino acid substitutions, incorporation of non-natural amino acids, and enzymatic drug attachment. Currently, a third generation of ADCs is in development. This study presents an overview of 12 available ADCs, reviews 71 recent research papers, and analyzes 128 clinical trial reports. The overarching objective is to gain insights into the prevailing trends in ADC research and development, with a particular focus on emerging frontiers like potential targets, linkers, and drug payloads within the realm of cancer treatment.

Background/Objectives: Our research introduces a novel screening method to identify antibodies that can suppress cell proliferation and induce apoptosis. Methods: By using an autocrine signaling system with lentivirus, we developed an antibody screening method based on FACS sorting assays and cell cycle analysis to inhibit tumor growth in vitro. This approach is particularly well suited for studying tumor suppressors. Inducing the G0 phase in tumor cells with specific antibodies may arrest their growth permanently or trigger apoptosis. The cell cycle is composed of tightly regulated phases for cell growth and division, with tumorigenesis or apoptosis occurring when these regulatory mechanisms fail. Results: In our study, we identified RACK1 as a key regulator of cancer cell growth. The H9 antibody against RACK1 selected from a human antibody library effectively suppressed cell proliferation by inhibiting RACK1 function. Conclusions: These findings suggest that RACK1 plays a crucial role in tumor cell cycling and could represent a novel therapeutic target for cancer treatment. Although RACK1 is recognized as a significant target protein in various tumors, no commercial therapeutic agents currently exist. Our results suggest that the H9 antibody could be a promising candidate for the development of novel cancer therapies.