Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:EXPT01586 (G418)
 2,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have produced a high-affinity chimeric anti-colorectal carcinoma antibody, ccM4, chimerized in both heavy and light chains by the construction of two expression vectors, the chimeric heavy-chain expression vector mpSV2neo-EP1-Vm4Cr1 and chimeric light-chain vector mpSV2gpt-EP1-VKCK. These vectors contained the neo or gpt gene as a selection marker, the murine immunoglobulin promoter and enhancer (EP1), the genomic DNA fragments of human immunoglobulin constant region (CK and C gamma 1), and murine cDNA fragments of VH and VK region amplified and cloned directly from the B72.3 hybridoma RNA by the polymer chain reaction technique. These two vector DNAs were sequentially transfected into the SP2/0Ag14 cell line. Transfectants were selected in media containing both G418 and mycophenolic acid. The ccM4 antibody was purified from transfectant supernatants with positive binding reactivity for the TAG72 antigen on a protein A column. We demonstrated that ccM4 antibody retained the same high binding reactivity for the TAG72 antigen as its counterpart, the high-affinity chimeric heavy-chain cB72.3m4 antibody. The ccM4 antibody bound specifically to human colon cancer cells, displayed biodistribution patterns similar to cB72.3m4 antibody, and mediated effective antibody-dependent cellular cytotoxicity to human OVCAR3 tumor cells. Therefore, the high-affinity chimeric ccM4 antibody should be useful in cancer immunotherapy.
 ...
PMID:Construction and characterization of a high-affinity chimeric anti-colorectal carcinoma antibody ccM4. 147 71

A mouse/human chimeric antibody cACT19 derived from the murine ACT19 antibody was constructed; it recognizes an epitope different from the sialosyl-Tn on the TAG72 antigen as defined by the B72.3 antibody. This chimeric cACT19 antibody was constructed by using two expression vectors, the heavy chain expression vector mpSV2neo-EP1-VHC gamma 1 and the light chain expression vector mpSV2gpt-EP1-VKCK. These vectors contain the following: (i) the neo or gpt gene as a selection marker, (ii) the murine immunoglobulin promoter and enhancer (EP1), (iii) the genomic DNA fragments of human immunoglobulin constant region (CK and C gamma 1) and (iv) the murine cDNA fragments of VH or VK region cloned from the murine ACT19 cDNA library. These two vector DNAs were sequentially transfected into the SP2/0Ag14 cell line. Transfectants were selected in media containing both G418 and mycophenolic acid. The chimeric cACT19 antibody was purified from the transfectant supernate by Protein A Sepharose chromatography. We confirmed that the chimeric cACT19 antibody was reactive for an epitope that differed from the sialosyl-Tn on the TAG72 antigen. This was achieved by using the TAG72-binding inhibition ELISA utilizing various monosaccharides and disialyllato-N-tetraose with the latter containing the NeuAc2-6 alpha Ga1NAc structure. The immunohistochemical double-staining technique provided further evidence of the difference between the epitope defined by the chimeric cACT19 antibody and the sialosyl-Tn epitope by illustrating complementary as well as noncomplementary expression of these two epitopes in different areas of colon carcinoma tissues. We also demonstrated that the chimeric cACT19 antibody displayed much more effective ADCC and CDC for the human OVAR3 tumor cells than the murine ACT19 antibody. Therefore, the mouse/human chimeric anti-colorectal carcinoma cACT19 antibody may prove to be useful in cancer immunotherapy in its own right, or especially when used in combination with the chimeric B72.3 antibody.
 ...
PMID:Recombinant mouse/human chimeric anti-colorectal carcinoma antibody cACT19. 775 75