Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have engineered a cysteine residue at position 442 (EU/OU numbering) in the third constant domain (C(H)3) of the heavy chain of several IgGs with different specificities, isoforms, and variants with the intent to introduce a site for chemical conjugation. The variants were expressed in NS0 mouse myeloma cells, where monomeric IgG is the major form and formation of aggregate was minimal. Monomeric IgG contained no free thiol; however, it was discovered that the engineered thiols were reversibly blocked and could be reduced under controlled conditions. Following reduction, reactive thiol was conjugated with a cysteine-specific bifunctional chelator, bromoacetyl-TMT to a humanized 323/A3 IgG4 variant. Conjugation had no significant effect on antibody affinity. To prove that the conjugation was site-specific, an antibody-TMT conjugate was labeled with lutetium-177 and subjected to peptide mapping followed by sequence analysis. Glu-C digestion demonstrated that 91% of the label was recovered in the COOH-terminal peptide fragment containing the engineered cysteine.
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PMID:Site-specific conjugation on serine right-arrow cysteine variant monoclonal antibodies. 1088 May 7

Mucin1 (MUCI) is a class of high molecular weight glycoproteins found in the cell membranes of human epithelial cells. Epithelial glycoprotein 40 (EGP40) is a homophilic cell-cell adhesion molecule and expressed on the surface of most simple epithelial cells and the majority of carcinomas. We analyzed the expression of MUC1 and EGP40 in human bone marrow (BM) and peripheral blood (PB) by reverse transcriptase polymerase chain reaction (RT-PCR) and immunocytochemistry (ICC). Eight BM and 95 PB samples from healthy donors, 39 BM and 17 PB samples from patients with haematological malignancies and 45 BM samples from patients with breast cancer were analyzed. MUC1 mRNA and EGP40 mRNA and protein were detected in BM samples and PB samples from healthy donors and from patients with multiple myeloma (MM), non-Hodgkin's lymphoma (NHL) and chronic myelogenous leukaemia (CML). The positive cells showed erythroblast-like and plasmacell-like morphology by immunocytochemistry. The MUC1 and EGP40 nested PCR were positive in 83.3% (10/12) and in 100% (33/33) respectively of BM from patiens with breast cancer who had no evidence of distant metastases. It is concluded that MUC1 and EGP40 is expressed in haematopoietic tissues and haematological malignancies. Therefore, MUC1 and EGP40 expression as a marker for detection of breast cancer cells and micrometastatic epithelial cells in BM and PB is not specific using RT-PCR technique and immunocytochemistry.
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PMID:Evaluation of MUC1 and EGP40 in bone marrow and peripheral blood as a marker for occult breast cancer. 1120 3

We are developing recombinant polyclonal antibody libraries (PCALs) reactive to human colorectal cancer cells as an anti-cancer therapeutic approach. To test the hypothesis that PCALs with preferential recognition of tumor cells as compared to normal cells could be generated, a Fab phage display library reactive to human colorectal cancer cell lines was absorbed with normal human blood cells. ELISA analysis of the absorbed Fab phage display library showed that 70% of tested clones reacted to colorectal cancer cells. Reactivity of the library to blood cells was reduced 4-10-fold, with many clones unreactive to one or more of the blood cell types. DNA fingerprint analysis of colorectal cancer-binding clones showed that the absorbed library remained polyclonal. The H and L chain V region gene pairs of the absorbed library were transferred in mass from the Fab phage display vector to a mammalian vector and expressed as IgG following transfection into Sp2/0 myeloma cells. ELISA analysis showed that 79% of transfectants expressed IgG and of those 74% were positive for binding to the SW480 human colorectal cancer cell line. A template of 95 SW480-reactive wells was assembled, designated Lib-Col2.1, and IgG purified from a consolidated mass culture. The purified Lib-Col2.1 IgG was compared to the clinically used anti-colorectal cancer mAb 17-1A, by ELISA and flow cytometry, for binding density on SW480 colorectal cancer cells and on normal human blood cells. The results showed that Lib-Col2.1 bound to SW480 cells at higher density than mAb 17-1A and that its binding to normal human blood cells was reduced 2.4-24-fold relative to an unabsorbed anti-SW480 serum. Furthermore, Lib-Col2.1 was more effective than mAb 17-1A at inhibiting the growth of SW480 cells in culture. These results suggest that a polyclonal antibody library with preferential reactivity to cancer cells as compared to normal cells could be generated.
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PMID:Generation and preliminary characterization of an antibody library with preferential reactivity to human colorectal cancer cells as compared to normal human blood cells. 1501 88


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