[Effect of targeting treatment of mitomycin C immunoconjugate on stomach neoplasm].
An anti-gastric cancer monoclonal antibody MGb2-mitomycin C conjugate via dextran T-70 as intermediate (MGb2-PAD-MMC) was produced, and 28-30 g molecules of MMC were introduced into 1 g molecule of MGb2. Ninety-six hours after ip of 125I-MGb2-PAD-MMC (1.48 MBq/22 micrograms MGb2 per mouse) to nude mice bearing human gastric cancer SGC-7901, the tumor tissue:blood (T/NT) radioactivity ratio was 2.6, very much higher than that of the control 125I-normal IgG-PAD-MMC group (T/NT = 0.20). Single photo computed tomography imaging confirmed the results of biodistribution study. MGb2-PAD-MMC exhibited selective killing action on the SGC-7901 cells in vitro, which was considered to be mediated by monoclonal antibody MGb2. Nude mice inoculated with SGC-7901 xenograft in bilateral subrenal capsule were treated by MMC (ip), human recombinant interferon-alpha (Hu-IFN-alpha im), MGb2-PAD-MMC (ip) and MGb2-PAD-MMC+Hu-IFN-alpha daily for 5 d beginning 4 h after inoculation. The efficacy of the reagents estimated by the reduction of tumor size and calculated by T/C (%), was 28.3%, 16.4%, 47.8%, and 83.1%, respectively. These results demonstrated that the antitumor effect of MGb2-PAD-MMC was superior to free MMC, and that the Hu-IFN-alpha might further enhance the action of MGb2-PAD-MMC.
Chen
L J
LJ
Shanghai Institute of Materia Medica, Chinese Academy of Sciences.
Zhang
S Y
SY
Zhang
J L
JL
Zhang
Z
Z
Li
S
S
Chen
M
M
Zhang
X Y
XY
Chen
X T
XT
D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000818:Animals; D000911:Antibodies, Monoclonal; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D007370:Interferon Type I / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016685:Mitomycin / Q000627:therapeutic use*; D011994:Recombinant Proteins; D013274:Stomach Neoplasms / Q000473:pathology / Q000628:therapy*; D013370:Subrenal Capsule Assay; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D007370:Interferon Type I; D011994:Recombinant Proteins; D016685:Mitomycin