Immunotargeting chemotherapy for AFP-producing pediatric liver cancer using the conjugates of anti-AFP antibody and anti-tumor agents.
The effect of immunotargeting chemotherapy for hepatoblastoma (HB) and hepatocellular carcinoma (HCC) following the application of adriamycin (ADM) or cis-platinum conjugated with anti-alpha-fetoprotein (AFP) antibody was evaluated experimentally and clinically. The conjugate was made from mouse monoclonal antihuman AFP antibody linked to ADM or CDDP, with a weight ratio of 2.5:1 via a dextran bridge. Experimentally, AFP-producing human HCC transplanted subsequently on nude mice was used. A mixture of the antibody and ADM or CDDP was prepared with the same ratio. Each drug was injected intraperitoneally, three times at the total dose of 14.4 mg/kg as ADM and one time at the dose of 8 mg/kg as CDDP. Tumor growth was inhibited significantly in the conjugate group compared with the other mixture group, the ADM or CDDP group, and the control group. Clinically, the conjugates were administered intraarterially in 4 cases (2 HBs and 2 HCCs) and intravenously in one case (1 HB). ADM and CDDP conjugated with anti-AFP antibody were used in 2 cases and 3 cases, respectively. Antitumor effects from the viewpoint of volume suppression rate showed partial response in 2 cases and no change in 3 cases. The immunotargeting chemotherapy using anti-AFP monoclonal antibodies may be a promising method for treatment of malignant epithelial liver cancer in children.
Hata
Y
Y
First Department of Surgery, Hokkaido University School of Medicine, Sapporo, Japan.
Takada
N
N
Sasaki
F
F
Abe
T
T
Hamada
H
H
Takahashi
H
H
Uchino
J
J
Tsukada
Y
Y
D000293:Adolescent; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007223:Infant; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D011379:Prognosis; D000509:alpha-Fetoproteins / Q000096:biosynthesis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000509:alpha-Fetoproteins; C055423:didimethylsulfoxide dichloroplatinum(II); D004317:Doxorubicin