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Biomedical subjects

S U Shin

Publications and source records attributed to S U Shin.

9 recordsLinked to original sources
PubMed1992

Genetically engineered antibodies: progress and prospects.

Techniques of genetic engineering and expression have been applied to the production of antibodies in a variety of expression systems. Novel antibodies have been produced with a variety of modifications: as chimeric antibodies, as "humanized" antibodies, with catalytic groups, as bifunctional or fusion proteins, and as functional fragments such as Fabs or Fvs. The domain structure of the antibody is favorable to such manipulation; the novel proteins often retain their antibody-derived activity and acquire new properties as well. Chimeric and complementarity-determining region (CDR)-grafted antibodies have been effective in immunotherapy, but problems of immunogenicity remain. Combinatorial libraries produced in bacteriophage may present an alternative to animal immunization as a source of antigen-binding specificities. Structural and mutational analysis of variable regions is providing useful information about the requirements of the variable region for antigen binding. Careful analysis and comparison of effector functions among immunoglobulin isotypes may be applied to the design of effective therapeutic antibodies.

Animals↗
PubMed1992

Structural and functional properties of mouse-human chimeric IgD.

A gene encoding mouse-human chimeric secreted IgD was constructed using the rearranged murine variable region specific for the hapten dansyl and the genomic gene sequences for the constant region of the heavy (H) chain of human IgD. When expressed with the dansyl-specific chimeric light (L) chain, chimeric IgD specific for the hapten dansyl was synthesized and secreted as an H2L2 molecule. The pathway of assembly was H + L----HL----H2L2. The chimeric IgD heavy chain contains three N-linked carbohydrate moieties; one of these appears to be added co-translationally, and the other two appear to be added post-translationally. In secreted chimeric IgD some of the N-linked carbohydrate remains in the high mannose form. The chimeric IgD heavy chain also contains O-linked carbohydrate, which is added at the time of secretion. Inhibition of N-linked glycosylation with tunicamycin halts assembly at the HL half-molecule stage and prevents secretion. Like natural human IgD, the chimeric IgD binds to and upregulates the IgD receptor (IgD-R) on human peripheral blood T cells, and it is equivalent to human myeloma IgD in the competitive inhibition of rosette formation between IgD-R-bearing cells and IgD-coated Ox-RBC, Cross-linking by dansyl-BSA is needed for the chimeric IgD in soluble form to cause IgD-R upregulation.

Animals↗
PubMed1991

Instability of immunoglobulin genes in S107 cell line.

Somatic mutation occurs frequently in rearranged and expressed immunoglobulin variable region genes in vivo. In contrast, V region hypermutation seldom occurs in antibody-forming cells in culture. The S107 mouse myeloma cell line is one of the few cell lines that has been observed to generate V region mutations frequently and spontaneously in vitro. Detailed examination reveals that both the S107 tumor and the cell line derived from it contain and express a duplicated heavy-chain gene. In culture, only one of the two heavy-chain genes undergoes both V and C region mutation, and variants with complex phenotypes and genotypes arise as a result of mutation and segregation of these duplicated genes.

Animals↗
PubMed1991

Chimeric antibody: potential applications for drug delivery and immunotherapy.

Antibodies, because of their inherent specificity, seem ideal agents for recognizing and destroying malignant cells. When monoclonal antibodies became available, they appeared ideal candidates for use as anti-cancer drugs. However, monoclonal antibodies as currently constituted still have certain inherent limitations. Transfectomas provide an approach to overcoming some of these limitations. Genetically engineered antibodies can be expressed following gene transfection into lymphoid cells. One of the major advantages of expressing genetically engineered antibodies, is that one is not limited to using antibodies as they occur in nature. In particular, non-immunoglobulin sequences can be joined to antibody sequences creating multi-functional chimeric antibodies. Creation of a family of multi-functional chimeric antibodies with a growth factor joined to a combining specificity may be useful in targeting therapy to malignant cells and delivering drugs into specific locales in the human body. Presence of the growth factor may facilitate transcytosis of chimeric antibody across the blood-brain barrier using growth factor receptors. These novel chimeric antibodies constitute a new family of immunotherapeutic molecules for cancer therapy.

Animals↗
PubMed1990

Expression and characterization of an antibody binding specificity joined to insulin-like growth factor 1: potential applications for cellular targeting.

To create antibody molecules with improved functional properties, a growth factor (insulin-like growth factor 1, IGF1) was used to replace the constant region of a chimeric mouse-human IgG3 anti-dansyl antibody. The chimeric heavy chain was expressed with an anti-dansyl-specific chimeric kappa light chain. The IgG3-IGF1 chimeric protein retained its specificity for the antigen dansyl. The chimeric proteins bound to the IGF1 receptors of the human lymphoblast IM-9, albeit with reduced affinity, and elicited some of the same biologic effects (increased glucose and amino acid uptake) in human KB cells as did human IGF1, but with reduced specific activity. The reduced affinity and biologic activity may result from several things: the presence of the unprocessed IGF1 moiety, the large size of the IgG3-IGF1 chimeric protein (160 kDa) compared with IGF1 (7 kDa), and three amino acid substitutions in rat IGF1 compared with human IGF1, which may lead to decreased affinity for the human IGF1 receptor. The chimeric proteins show that it is feasible to produce a new family of immunotherapeutic molecules targeted to growth factor receptors.

Amino Acid Sequence↗