[Use of monoclonal antibody-pinyangmycin conjugate in experimental regional targeting therapy of tumor].
McAb 3A5, a rat monoclonal antibody, was linked to pingyangmycin (PYM), an antitumor antibiotic identical to bleomycin A5 currently in clinical use, employing Dextran T-40 as an intermediate agent. The 3A5-PYM conjugate retained complete immunoreactivity of McAb 3A5. Determined by clonogenic assay with colon cancer HT-29 cells, the IC50 values for 3A5-PYM conjugate and free PYM were 0.6 mumol.L-1 and 10.2 mumol.L-1, respectively. Hepatoma H22 ascites was transplanted into the peritoneal or thoracic cavity of mice. On the next day, 3A5-PYM or PYM, were injected into the cavity. Therapeutic effect was evaluated on the survival time of mice. For intraperitoneal tumor, the ILS(%) values were 238% for 3A5-PYM and 40% for PYM. For intrapleural tumor, the ILS(%) values were 384% for 3A5-PYM and 66% for PYM. Murine hepatoma H22 was transplanted s.c. into mice and 3A5-PYM conjugate or free PYM were injected peritumorally. As determined by antimicrobial assay, the administration of 3A5-PYM showed higher concentration and longer retention time in the tumor than that of free PYM. Tumor fragments of human colon cancer HT-29 were transplanted s.c. into nude mice. Then 3A5-PYM or PYM was injected i.v., i.p. or pt (peritumorally) 3 days after inoculation, twice a week, with a total of 7 injections. Tumor growth inhibition was evaluated 4 weeks later. The inhibition rates on the growth of colon cancer xenografts were as follows: (1) for i.v. route, 58% by PYM, 79% by 3A5-PYM; (2) for i.p. route, 52% by PYM, 61% by 3A5-PYM; and (3) for pt route, 73% by PYM, 96% by 3A5-PYM. These results indicate that 3A5-PYM conjugate is highly effective against targeted human cancer xenograft and mouse tumor when administered peritumorlly or intracavitarily.
Wang
W G
WG
Institude of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050.
Xu
L N
LN
Zhang
S H
SH
Xue
Y C
YC
Zhen
Y S
YS
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001761:Bleomycin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005260:Female; D019073:HT29 Cells; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D001761:Bleomycin; C021771:zhengguangmycin