Abstract:Gelatinases are overexpressed in several types of maligancies and tumor stromal cells. Lidamycin is an enediyne antitumor antibiotic, which is composed of an apoprotein (LDP) and an active chromophore (AE). It is known that the heavy-chain complementarity-determining region-3 (CDR3) domain of scFv is important in antibody affinity. The aim of this study was to prepare the enediyne-energized fusion proteins with a heavy-chain CDR3 domain of anti-gelatinases scFv and lidamycin, and to evaluate their antitumor ef… Show more
“…Though, LDM is a potent ''warhead'' drug, it lacks the targeting function resulting in systemic toxicity. Previous studies have shown that LDM-related enediyneenergized fusion proteins presented stronger inhibitory activity in tumor targeting therapy [36][37][38]. In this study, we conjugated the anti-CD19(Fab) antibody with LDM by genetic engineering to generate ADC anti-CD19(Fab)-LDM, which has a stable structure and delivers drug to the target cells.…”
The present study demonstrated that the genetically engineered antibody anti-CD19(Fab)-LDM exhibited enhanced cytotoxicity compared to LDM alone. One of the most powerful advantages of anti-CD19(Fab)-LDM, however, is that it can be internalized within the cells and carry out cytotoxic effects. Therefore, anti-CD19(Fab)-LDM may be as a useful targeted therapy for B-cell lymphoma.
“…Though, LDM is a potent ''warhead'' drug, it lacks the targeting function resulting in systemic toxicity. Previous studies have shown that LDM-related enediyneenergized fusion proteins presented stronger inhibitory activity in tumor targeting therapy [36][37][38]. In this study, we conjugated the anti-CD19(Fab) antibody with LDM by genetic engineering to generate ADC anti-CD19(Fab)-LDM, which has a stable structure and delivers drug to the target cells.…”
The present study demonstrated that the genetically engineered antibody anti-CD19(Fab)-LDM exhibited enhanced cytotoxicity compared to LDM alone. One of the most powerful advantages of anti-CD19(Fab)-LDM, however, is that it can be internalized within the cells and carry out cytotoxic effects. Therefore, anti-CD19(Fab)-LDM may be as a useful targeted therapy for B-cell lymphoma.
Calicheamicin, the payload of the antibody-drug-conjugates (ADCs) gemtuzumab ozogamicin (Mylotarg®) and inotuzumab ozogamicin (Besponsa®), belongs to the class of enediyne natural products. Since the isolation and structural determination of the neocarzinostatin chromophore in 1985, the enediynes have attracted considerable attention for their value as DNA damaging agents in cancer chemotherapy. Due to their non-discriminatory cytotoxicity towards both cancer and healthy cells, the clinical utilization of enediyne natural products relies on conjugation to an appropriate delivery system, such as an antibody. Here, we review the current landscape of enediynes as payloads of first-generation and next-generation ADCs.
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