Studies Of The Antitumor Efficacy Of Monoclonal Antibody Immunoconjugates Directed Against Type Ⅳ Collagenase And The Estalishment Of Screening Models For Inhibitors Of The Enzyme

Matrix metalloproteinases (MMPs) has been viewed as a promising target in tumor therapy in recent years due to their key role in tumor growth, angiogenesis, invasion and metastasis. MMP inhibitors, including both the natural tissues MMPs inhibitors (TIMPs) and synthetic low molecular MMPs inhibitors showed the potency of inhibiting tumor growth and metastsis. Type â…£ collagenase is an important member of MMPs family which can destroy the integrity of basement membrane and extracellular matrix through the degrading of Type â…£ collagen, thus facilitate the process of tumor invasion and metastasis. Also, the expression and secretion of Type â…£ collagenase is highly elevated in tumor cells and adjacent interstitial tissue, especially in malignancy with high potential of invasion and metastasis. Studies using Type â…£ collagenase as a molecular target have achieved a lot in tumor therapy especially in the control of tumor metastasis. Based on this, the study of using Type â…£ collagenase inhibitors to control its activity and the study of using anti-Type â…£ collagenase monoclonal antibody as a vector to realize targeting antitumor drugs to the tumor site are two prospective methods for malignancy therapy. And the latter may have dual effects due to the antibody neutralization of enzyme activity and the specific cell-killing effect of antitumor drugs. In this study we developed research on both of the two methods mentioned above. The studies focus on the below fields.1. The preparation of immunoconjugate composed of lidamycin and monoclonal antibody 3D6 and the evaluation of its antitumor effectsMurine monoclonal antibody 3D6 can bind to Type â…£ collagenase specifically. The immunoconjugate composed of mAb 3D6 and pingyangmycin have shown some striking results in tumor therapy. Lidamycin (LDM, also named as C1027), conjugated with mAb 3D6 also exhibited preliminary results. Recently, the approval of a new immunoconjugate consisting of radionuclides Yttrium-90 and an intact murine anti-CD20 antibody by FDA...