[Experimental studies on therapeutic effect of rat monoclonal antibody-bleomycin A6 conjugate against human colorectal cancer].
Bleomycin A6 (A6), a single component of bleomycin complex, is highly active against human colon and cecum cancer cells in vitro and xenografts in nude mice. R19, a rat monoclonal antibody against human cecum cancer Hce-8693 cells, was linked to A6. R19-A6 conjugate retained complete activity of McAb R19 and 10% activity of A6. As determined by clonogenic assay with human cecum cancer Hce-8693 cells for 1 hour exposure. The 50% inhibitory concentration (IC50) values for R19-A6, A6 and M3-A6 (conjugate of irrelevant Mc-A6) were 0.019, 1.05 and 1.00 mumol/L, respectively. The effect of the conjugate R19-A6 was 55-fold stronger than that of free A6 and 53-fold than irrelevant conjugate M3-A6. Clonogenic assay with human colon cancer HT-29 cells showed that the IC50 values were 0.078 mumol/L and 4.0 mumol/L for R19-A6 and free A6, respectively. The cytotoxicity to Hce-8693 and HT-29 cells was markedly blocked by unconjugated McAb R19 but not by irrelevant McAb MARK-3. The R19-A6 conjugate exerted 90% inhibition on the growth of cecum cancer Hce-8693 xenografts in nude mice, whereas equivalent doses of free A6, R19 plus A6 mixture and M3-A6 showed 52%, 34% and 48% inhibition, respectively. Histopathological examination showed no toxic changes in the heart, lung, liver, kidney and bone marrow in the R19-A6 conjugate treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Deng
Y C
YC
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing.
Zhen
Y S
YS
Zheng
S
S
Jiang
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001761:Bleomycin / Q000494:pharmacology / Q000627:therapeutic use* / Q000031:analogs & derivatives; D002430:Cecal Neoplasms / Q000473:pathology / Q000628:therapy*; D003110:Colonic Neoplasms / Q000473:pathology / Q000628:therapy*; D005260:Female; D000922:Immunotoxins / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; C052656:bleomycin A6; D001761:Bleomycin