Biomaterial Database

[Biodistribution of monoclonal antibody and Fab fragment and antitumor effect of their conjugates on hepatoma xenografts]. 1994

J Li, and Y Zhen, and Z Yang

Institute of Medicinal Biotechnology, CAMS, Beijing.

McAb 3A5, a rat monoclonal antibody directed against human hepatoma cells, and its Fab fragment were compared on their biodistribution and the therapeutic effects of their conjugates linked to C1027, a highly potent antitumor antibiotic, on the growth of human hepatoma xenografts in nude mice. Biodistribution study with 125I-labeled McAb 3A5 and its Fab fragment in hepatoma-bearing nude mice revealed that ID%/g values of McAb 3A5 were higher than those of the Fab fragment in tumor, liver, spleen and kidney; however, the T/NT ratios of Fab were higher than those of McAb 3A5. Imaging study with 131I-3A5 and 131I Fab showed that clear images of the tumor emerged 12h after injection of Fab and 40 h after that of McAb 3A5. IC50 values for McAb-C1027 and Fab-C1027 were 4.2 x 10(-14) mol/L, 8.6 x 10(-16) mol/L, respectively. Fab-C1027 conjugate was 49-fold more potent than McAb-C1027. Therapeutic effect of the conjugates was evaluated with hepatoma xenograft in nude mice. When treatment started 3 days after sc transplantation of the tumor with equivalent dose of C1027, 0.15 mg/kg, i.v., x3, tumor inhibition rates for McAb-C1027 and Fab-C1027 conjugates were 68% and 66%, respectively. When the treatment started on day 10 after transplantation with 0.10 mg/kg, i.v., x6, tumor inhibition rates for McAb-C1027 and Fab-C1027 conjugates were 24% and 54%, respectively. The results showed that compared with the intact McAb, Fab fragment displays higher specificity in biodistribution and exerts stronger inhibitory effect on the growth of established tumor xenografts.

UI	MeSH Term	Description	Entries
D007140	Immunoglobulin Fab Fragments	Univalent antigen-binding fragments composed of one entire IMMUNOGLOBULIN LIGHT CHAIN and the amino terminal end of one of the IMMUNOGLOBULIN HEAVY CHAINS from the hinge region, linked to each other by disulfide bonds. Fab contains the IMMUNOGLOBULIN VARIABLE REGIONS, which are part of the antigen-binding site, and the first IMMUNOGLOBULIN CONSTANT REGIONS. This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.	Fab Fragment,Fab Fragments,Ig Fab Fragments,Immunoglobulins, Fab Fragment,Fab Immunoglobulin Fragments,Immunoglobulin Fab Fragment,Immunoglobulins, Fab,Fab Fragment Immunoglobulins,Fab Fragment, Immunoglobulin,Fab Fragments, Immunoglobulin,Fragment Immunoglobulins, Fab,Fragment, Fab,Immunoglobulin Fragments, Fab
D008113	Liver Neoplasms	Tumors or cancer of the LIVER.	Cancer of Liver,Hepatic Cancer,Liver Cancer,Cancer of the Liver,Cancer, Hepatocellular,Hepatic Neoplasms,Hepatocellular Cancer,Neoplasms, Hepatic,Neoplasms, Liver,Cancer, Hepatic,Cancer, Liver,Cancers, Hepatic,Cancers, Hepatocellular,Cancers, Liver,Hepatic Cancers,Hepatic Neoplasm,Hepatocellular Cancers,Liver Cancers,Liver Neoplasm,Neoplasm, Hepatic,Neoplasm, Liver
D008807	Mice, Inbred BALB C	An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research.	BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008819	Mice, Nude	Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.	Athymic Mice,Mice, Athymic,Nude Mice,Mouse, Athymic,Mouse, Nude,Athymic Mouse,Nude Mouse
D009368	Neoplasm Transplantation	Experimental transplantation of neoplasms in laboratory animals for research purposes.	Transplantation, Neoplasm,Neoplasm Transplantations,Transplantations, Neoplasm
D010455	Peptides	Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS.	Peptide,Polypeptide,Polypeptides
D006528	Carcinoma, Hepatocellular	A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.	Hepatocellular Carcinoma,Hepatoma,Liver Cancer, Adult,Liver Cell Carcinoma,Liver Cell Carcinoma, Adult,Adult Liver Cancer,Adult Liver Cancers,Cancer, Adult Liver,Cancers, Adult Liver,Carcinoma, Liver Cell,Carcinomas, Hepatocellular,Carcinomas, Liver Cell,Cell Carcinoma, Liver,Cell Carcinomas, Liver,Hepatocellular Carcinomas,Hepatomas,Liver Cancers, Adult,Liver Cell Carcinomas
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000617	Aminoglycosides	Glycosylated compounds in which there is an amino substituent on the glycoside. Some of them are clinically important ANTIBIOTICS.	Aminoglycoside
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia