The Construction Of An Engineered And Energized Fusion Protein Consisting Of Lidamycin And Anti-Type Ⅳ Collagenase Monoclonal Antibody And Its Antitumor Activity

With the invention of the hybridoma technology that allows production of monoclonal antibody (mAb), a new era of biological therapy for invasive and metastasis cancer has been initiated. A variety of mAbs, with high specificity and affinity for their target antigens, have been utilized in the recent decades for delivery of anticancer agents such as drugs, enzymes, radionuclides, or toxins in cancer therapy. The specificity of mAb to unique epitope is the key to antitumor activity of antibody-based therapeutics. Because of the specificity of mAbs directed to mutant or overexpressed oncogenes, and other tumor-associated antigens, antibody-based drugs have been achieved by tailored making according to various needs. The results of the research on mAbs have shown that their specificities mainly presents high special affinity, selective cytotoxicity to tumor cells in vitro, and targeting distribution in tumors and more effective therapy. Moreover, the antibody-based therapy for cancer has been in favor of offering promise as a technical platform and obtaining a variety of high potent agents for clinical application. Therefore, utilizing chemical method for immunoconjugates or DNA recombinant technology for scFv-fusion protein, miniature and high powerful agents specially targeting to tumors have been made for various needs. Since the promising potent of antibody-based therapeutics has been revealed, this studies focused on characterizations of novel molecular targets, construction and biological analysis of antibody-based drugs.1. The characterization of mAb 3G11 and the antitumor effects of immunoconjugate 3G11-LDMType IV collagenases, also termed gelatinases, including MMP-2 of 72 kDa and MMP-9 of 92 kDa play an extremely important role during tumor growth and progression and display as an attractive target for monoclonal antibody-directed therapy. Type IV collagenases degrade type IV collagen which is the major component of basement membrane and other collagens, and destroy the integrality of basement membrane and extracellular matrix, which is in favor of the invasion and metastasis of tumor cells. In addition, the activities of type IV collagenases are higher in endothelial cells stimulated by angiogenesis factors than normal cells. Inhibition of the activities of type IV collagenase may inhibit tumor invasion and metastasis, and angiogenesis. The...