Immunoscintigraphy Of MAb Or Its Fab' Fragment And The Preparation And Antitumor Efficacy Of Their Immunoconjugates With Pingyangmycin

Type IV collagenase, a key member of matrix metalloproteinases (MMPs) family, plays an important role in many steps of tumor development, including proliferation, invasion, metastasis, and angiogenesis. Studies focusing on type IV collagenase as a molecular target have made great achievements in cancer therapy, and several candidates of small molecule MMP inhibitors are under clinical investigation. Monoclonal antibody (mAb) has been viewed as the "magic bullet" in treating tumors due to its high specificity, high avidity, tailor-made characters and the ability to deliver "warhead" effectors such as cytotoxic agents, radionuclides and toxins. Several therapeutic mAbs have been approved by FDA in recent years, revealing a bright future in targeted cancer therapy. In our previous work, a murine mAb directed against type IV collagenase had been established. It could specifically bind to the antigen and efficiently neutralize the enzyme activity. Also, chemo-immunoconjugates or fusion proteins based on the mAb and its fragments led to promising efficacy in experimental mice tumor models. In this study, we evaluated the specific localization of anti-type IV collagenase mAb 3G11 and its enzyme degraded Fab' fragment by radioimmunoscmtigraphy. On the other hand, we prepared two immunoconjugates composed of pingyangmycin (PYM) and mAb 3G11 or the Fab' fragment via poly-α-L-glutamic acid (PLG) intermediate carrier, and further studied their antitumor efficacy.1. Immunoscintigraphy and biodistribution of anti-type IV collagenase mAb 3G11 and its Fab' fragmentDevelopment of radioisotope technology has provided credible approaches in immunological and pharmacological evaluation of monoclonal antibodies. In our work, we radiolabeled the mAb 3G11 or its Fab' fragment with radioiodine, then determined their tumor-specific distribution in vivo by radioimmunoimaging.mAb 3G11 was prepared from ascites with hybridoma cells inoculated in BALB/c mice. Its purity reached to 95% after being purified by caprylic acid - ammonium sulphate precipitation...