Wang W G, Xu L N, Zhang S H, Xue Y C, Zhen Y S
Institude of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050.
Yao Xue Xue Bao. 1997 Sep;32(9):669-74.
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.
