چاپ صفحه |  صفحه نخست سامانه |  نویسندگان |  اطلاعات تفضیلی |  دانلود مقاله | دانشگاه علوم پزشکی تبریز |
| نویسنده | نفر چندم مقاله |
|---|---|
| رضا حسنی | اول |
| محمد رضا توحیدکیا | دوم |
| محمد رحمتی | سوم |
| عنوان | متن |
|---|---|
| کلمات کلیدی | ADC, CDC, B-cell malignancies, bispecific antibody, CD20, monoclonal antibody |
| خلاصه مقاله | Introduction Overexpression of a phosphoprotein antigen called CD20 in B-cell malignancies has provided targeting CD20 by monoclonal antibodies (mAbs) as a well-known and promising procedure. So far, several therapeutic anti-CD20 mAbs have been used for treatment of B-cell malignancies in clinic such as rituximab (Rituxan), ofatumumab (Arzerra), and obinutuzumab (GA-101), which mechanism of action in every case is different from others. The aim of this study is a comparison based on different mechanisms of action on Therapeutic anti-CD20 antibodies. Methods We searched the PubMed database and found that these antibodies are the most effective and therapeutic cases for lymphoma and leukemia cancers in related articles. We investigated about 30 original and review articles that several antigens such as CD19, CD20, CD22, and CD33 targeted by above mAb since 2010 to 2022. Afterward, we restricted our search and screened articles that were related to RTX, GA-101 and CD20 antigen. Results Rituximab accepted as a first generated antibody against CD-20. Then, engineering in the antibodies structure led to development of second and third generation, which second generation includes ofatumumab and obinutuzumab classify as third generation. Based on the mechanism of action anti-CD20 mAbs can be classified into the two classes of type I (rituximab and ofatumumab) and type II (Obinutuzumab). Type I antibodies are potent for the localization of CD20 into the large microdomains (lipid raft) within the plasma membrane by two mechanisms: Complement-Dependent Cytotoxicity (CDC) and moderate Antibody-Dependent Cell-mediated Cytotoxicity (ADCC) activity and induce weak indirect cell death. However, type II antibodies are more potent than type I because they induce homotypic adhesion by mitochondrial aggregation and direct strong cell death by releasing of lysosomal cathepsin in cytoplasm. Moreover, high ADCC and low CDC in type II are obvious. Since the CD20 antigen contains two extracellular large and small loops which the large loop is just targetable by RTX and GA-101. Thus, according to the results a comparison between RTX and GA-101 in phase III trial, GA-101 demonstrated superiority to RTX in non-Hodgkin Lymphoma (NHL) and chronic lymphocyte leukemia (CLL). However, adverse side effects such as early neutropenia has observed after screening the patients which treated by obinutuzumab. Conclusion Since treatment with full-length and different fragments of antibodies like Fab and SCFV were not successful, other engineered products such as bispecific antibodies and Antibody-drug conjugates (ADC) and also radiolabeled antibodies such as 90Y-ibritumomab and 131I-tositumomab against CD20 developed. Eventually, developing of the new engineered mAb, which are specific with high tolerance and low side effects is the fundamental aim for treatment of leukemia, lymphoma and other B-cell malignancies. |
| نام فایل | تاریخ درج فایل | اندازه فایل | دانلود |
|---|---|---|---|
| certification.pdf | 1402/04/08 | 167925 | دانلود |
| abstract.pdf | 1402/04/20 | 442828 | دانلود |
