When people are diagnosed with advanced cancer, surgery can remove the tumor but it can't stop the spread of the cancer cell. Numerous experiments and clinical trials have been carried out to find drugs for the treatment of cancer. And scientists have discovered the great potential of antibody-dependent cell-mediated cytotoxicity (abbreviated as ADCC) in inhibiting certain tumor cells. ADCC refers to the Fab fragment antibody that binds to the antigen epitope of the infected or tumor cells, and its Fc fragment binds to the FCR on the surface of the effector cells (including NK cells, macrophages, neutrophils, eosinophils, and dendritic cells) to mediate the direct killing of target cells by killer cells. In recent literature, Its importance in treating cancer cells and in gaining insight into their complex pathways has become a topic of increasing interest among medical researchers.

In the early 1960s, several independent researchers found that lymphocytes had the function of killing other cells, but the mechanism of their killing was unclear. In 1965, a researcher at the Karolinska Institute found a cell-killing effect when mice tumor cells were mixed with heat-inactivated rabbit serum immunized with tumor cells, and lymphocytes from unimmunized mice were added. At that time, they have come to view as the killing effect of lymphocytes was mediated by serum-induced aggregation. In the 1970s, researchers from the Canadian Red Cross Memorial Hospital MacLennan, Loewi and Harding discovered that the substance used for serum-mediated cell destruction was IgG antibody. This phenomenon of serum antibody-mediated cytotoxic damage that requires no other substances is known as antibody-dependent cell-mediated cytotoxicity.

When it comes to the 21st century, scientists have a rich understanding of the whole process of ADCC. At present, the mechanism of ADCC is used to detect and evaluate the efficacy of antibodies or target cells. Based on this mechanism, biologists have developed monoclonal antibodies that recognize different molecular targets, thereby inducing cytotoxic immune effector cells to clear virus-infected cells and tumor cells. Studies have shown that the combination of ADCC and some specific monoclonal antibodies (mAbs) can enhance anti-tumor function. And this approach is unique in combining a tumor-targeting therapy (the mAb), with an immune-enhancing therapy.

Previous research from Stanford School of Medicine has shown the combination of tumor-targeting mAbs and ADCC-enhancing immunomodulators is a promising treatment strategy for oncology patients. They believed that the applicability of this approach would increase as more tumor-associated antigens are identified and the activation pathways of the immune effectors are better understood.

Building upon previous research, in which a team from Georgetown University, designed and engineered antibodies with enhanced ADCC eliciting properties to improve outcomes in patients with limited responses to monoclonal antibody therapy. In their study, they not only examined FcγR polymorphisms, but also used patient samples from clinical trials to investigate the relative importance of ADCC to therapeutic success.

Also, the SOPHIA clinical trial of anti-HER2 mAb optimized for the Fc fragment successfully proved that enhanced ADCC efficacy does indeed contribute to the treatment of anti-antibody tumors. In patients with HER2-positive breast cancer who had previously received anti-HER2 treatment, this Fc fragment modified anti-HER2-monoclonal antibody combined with chemotherapy has significant advantages over trastuzumab in progression-free survival (PFS), reducing the risk of disease progression by 24%. This experiment affirmed that stronger enhanced ADCC can translate into survival benefits for patients.

Since 1997, several monoclonal antibodies have become the standard treatment for solid tumors and hematological malignancies. Targeted drugs that have been used in patients include rituximab, trastuzumab (TRAST), alenimab, cetuximab, panimab and ofatumumab. There is well-researched evidence that ADCC enhanced antibodies play a vital role in anti-cancer and provide unlimited potential in immunotherapy, thus opening up a new era of oncology treatment.

Since 2013, the U.S. Food and Drug Administration (FDA) and the European Union Drug Administration (European Medicines Agency) have approved thirty-one new monoclonal antibodies (mAb). By the end of 2017, a total of 57 monoclonal antibodies were used in the clinic. With the support of the government, the market demand is extremely huge. Several financial reports revealed that the antibody market had exceeded 98 billion US dollars in sales by December 2017, with an annual growth rate of 18.3% and a predicted valuation of 137-200 billion US dollars by 2022.


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