OBJECTIVE: To develop a novel monoclonal antibody (mAb) immunoconjugate with downsized-molecule and highly potent antitumor effects. METHODS: The mAb conjugate was prepared by linking @entity2964 (LDM), an antitumor antibiotic with extremely potent @entity137 , to mAb Fab' fragment. The molecular weight of Fab'-LDM was determined by non-reduced SDS-PAGE. The immunoreactivity of Fab'-LDM conjugate with @entity5 cells was detected by ELISA. The antitumor activity of the conjugate was determined by @entity98 assay, clonogenic assay, and animal model of transplantable @entity694 26' (C26) in @entity19 . RESULTS: The relative molecular mass of Fab'-LDM conjugate was approximately 65,000, suggesting a molar ratio of 1:1 between Fab' fragment and LDM in the conjugate. Fab'-LDM was reactive with @entity157 BEL-7402 and @entity694 26 cells, but not reactive with KB cells. The @entity137 of Fab'-LDM conjugate to BEL-7402 cells, the antigen relevant @entity5 cells, was 13-fold more potent than that of free LDM, while the @entity137 of Fab'-LDM conjugate against C26 cells was 5.5-fold more potent than that of free LDM. However, the @entity137 of Fab'-LDM conjugate to KB cells, the antigen irrelevant cells, was similar to that of free LDM. Given by 3 intravenous injections, on day 1, 4 and 7, Fab'-LDM conjugate at doses of 0.05 mg/kg, 0.1 mg/kg and 0.2 mg/kg markedly suppressed the growth of @entity694 26 in @entity19 by 80%, 92% and 94%, respectively, whereas free LDM at 0.1 mg/kg suppressed the growth by 77%. The survival time of @entity5 -bearing @entity19 was also increased by Fab'-LDM conjugate treatment. Fab'-LDM conjugate was more effective than equivalent unconjugated LDM (P < 0.01). CONCLUSIONS: The immunoconjugate composed of LDM and Fab' fragment that is characterized by downsized-molecule shows remarkable effectiveness against @entity5 growth.

[Antitumor effect of XXXX -containing monoclonal antibody immunoconjugate with downsized-molecule].

@entity137 :: ('MESH:D064420', 'Disease') :: ['cytotoxicity'] @entity2964 :: ('MESH:C058024', 'Chemical') :: ['lidamycin'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity98 :: ('CHEBI:53233', 'Chemical') :: ['MTT'] @entity157 :: ('MESH:D006528', 'Disease') :: ['hepatoma'] @entity694 :: ('MESH:D003110', 'Disease') :: ['colon carcinoma']
@entity2964 :: (MESH:C058024,Chemical) :: ['lidamycin']
