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)

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

Chimeric receptors that redirect effector cell function to tumor cells or virus-infected cells have received much attention. Given the high affinity of Fc(epsilon)RI for immunoglobulin E (IgE) and low serum IgE levels, redirection of effector cells using Fc(epsilon) receptor may provide a novel, versatile, and effective anti-tumor strategy. We have used a mouse perforin 5'-promoter to express a single-chain human Fc(epsilon) receptor in the mouse cytotoxic T lymphocyte cell line, CTLL-R8. Upon ligation of the chimeric Fc(epsilon) receptors by IgE, a signal for effector function is transmitted via the intracellular domain of CD3zeta. Selection in G418-containing medium produced CTLLR8 transfectant clones that: (1) expressed chimeric Fc(epsilon) receptor as determined by flow cytometry; (2) bound human IgE antibodies with high affinity as determined by Scatchard analysis; (3) specifically rosetted IgE-coated SRBC; (4) lysed target cells in IgE-mediated ADCC and reverse ADCC assays; and (5) retarded tumor growth in a Winn assay. Therefore these chimeric Fc(epsilon) receptors can effectively redirect cytotoxicity to tumor cells. Future efforts will assess the versatility and efficacy of these IgE-binding chimeric receptors to redirect killer cell function in animal tumor models.
 ...
PMID:The use of chimeric human Fc(epsilon) receptor I to redirect cytotoxic T lymphocytes to tumors. 897 74