The Fc portion of the mAb bind on the Fc receptor expressed on the effector immune cells, including natural killer (NK) cells, macrophages, and dendritic cells. The antigen-binding fragment determines the specificity of mAb. The functional part of mAbs includes the antigen-binding F(ab)2′ part and an Fc region. This treatment has a high specificity for tumor cells and thus has little or no side effects on the normal tissue. One of the most common forms of immunotherapy is the use of monoclonal antibodies (mAbs), designed to precisely influence the host response to tumor cells. Given the remarkable progress made with tumor immunotherapy, it was recently identified as a major breakthrough in clinical cancer treatment. Therefore, tumor immunotherapy comprises various techniques that aim to enhance intrinsic immune mechanisms to promote eradication of tumor cells. Furthermore, malignant cells induce immune dysregulation by down-regulation of ligands that are natural activators of immune cells. However, both in solid and hematological tumors, malignant cells aggregate and cultivate in a suppressive micro-environment, including hypoxia, low pH and inhibitory cytokines, and molecules, which is detrimental to the function of immune cells. In hematologic malignancies, the tumor cells are dispersed in the blood, bone marrow, and lymph nodes, which in principle facilitates access to tumors by immune cells to conduct eradication. One hallmark of this neoplastic disease is avoidance of immune destruction. Collectively, this study describes novel fully humanized anti-MUC1 antibodies that, especially after defucosylation, are promising therapeutic candidates for cellular immunotherapy.Ĭancer is still one of the leading causes of death around the globe. We show that endocytosis inhibitors augment the availability of MUC1-Tn/STn epitopes on tumor cells but do not further enhance ADCC in NK cells. Defucosylation of these newly developed anti-MUC1 antibodies further enhanced antigen-dependent cellular cytotoxicity (ADCC) mediated by NK cells. We confirmed that these antibodies specifically recognize tumor-associated MUC1 epitopes and can activate human NK cells in vitro. Herein, we describe the generation of fully humanized antibodies based on the murine 5E5 antibody, targeting the tumor-specific MUC1-Tn/STn epitope. Several anti-MUC1 antibodies have been tested for therapeutic applications in solid tumors thus far without clinical success. Mucin 1 (MUC1) is a highly glycosylated protein expressed in normal epithelial cells, while the under-glycosylated MUC1 epitope (MUC1-Tn/STn) is only expressed on malignant cells, making it an interesting diagnostic and therapeutic target. The binding of antibodies can have direct effects on tumor cells but also engages natural killer (NK) cells via their Fc receptor. Antibodies are commonly used in cancer immunotherapy because of their high specificity for tumor-associated antigens.
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