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11. |
Recent Developments in Catalytic Antibodies |
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International Reviews of Immunology,
Volume 10,
Issue 2-3,
1993,
Page 229-240
StewartJon D.,
BenkovicStephen J.,
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ISSN:0883-0185
DOI:10.3109/08830189309061698
出版商:Taylor&Francis
年代:1993
数据来源: Taylor
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12. |
Humanized Antibodies: Enhancing Therapeutic Utility Through Antibody Engineering |
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International Reviews of Immunology,
Volume 10,
Issue 2-3,
1993,
Page 241-250
JolliffeLinda K.,
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摘要:
The promise of antibody therapeutics has been greatly expanded by the development of monoclonal antibody technology and more recently antibody humanization. By transferring the mouse antibody binding site into a human antibody gene, we can engineer a“human antibody”which retains the specificity and biological effects of the original mouse antibody but has the potential to be nonimmunogenic in humans. Additionally, antibody effector functions can be improved through manipulation of the antibody constant region genes.We have produced a humanized version of OKT3 with human IgG4 and kappa constant regions. This antibody retains all of thein vitrocharacteristics of murine OKT3 including induction of cytokine release and T cell activation markers. Humanized OKT3 has an affinity of 1.4×109M−1relative to a 1.2×109M−1affinity of murine OKT3. Substitution of a glutamic acid for leucine at residue 235 in the antibody constant region abrogates FcR I binding and causes a marked reduction of T cell activation. The humanized FcR mutant of OKT3 has potential to be an improved therapeutic for transplantation and may have applications in autoimmune disease treatment.
ISSN:0883-0185
DOI:10.3109/08830189309061699
出版商:Taylor&Francis
年代:1993
数据来源: Taylor
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13. |
Antigenicity and Immunogenicity of Antigenized Antibodies. Studies on B and T Cells |
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International Reviews of Immunology,
Volume 10,
Issue 2-3,
1993,
Page 251-263
BillettaRosario,
ZanettiMaurizio,
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摘要:
This laboratory has been testing the possibility of using the complementarity-determining region (CDR) loops of the antibody molecule to express oligopeptide epitopes in an immunologically-accessible and conformationally-suitable way. The new process consists in grafting peptides epitopes derived from antigens other than immunoglobulins into antibody CDR loops [1], This process,“antibody antigenization,”utilizes the immunoglobulin fold as a scaffold to immobilize and present oligopeptide epitopes to the immune system as the integral part of the immunoglobulin molecule. Here we describe some of the initial results with antigenized antibodies (AgAbs).
ISSN:0883-0185
DOI:10.3109/08830189309061700
出版商:Taylor&Francis
年代:1993
数据来源: Taylor
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14. |
Engineered Immunoglobulin Molecules as Vehicles for T Cell Epitopes |
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International Reviews of Immunology,
Volume 10,
Issue 2-3,
1993,
Page 265-278
ZaghouaniHabib,
KuzoYukiko,
KuzoHiroshi,
MannNoelle,
DaianChristina,
BonaConstantin,
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摘要:
The variable regions (V) of immunoglobulins (Ig) bear antigenic determinants that can stimulate both humoral and cellular immune responses subsequent to hetero, allo or iso-immunization. The expression of these determinants by Igs usually correlates with the presence of specific amino acid residues within the CDR loops of the V regions. Since the CDR loops varies in length, we reasoned that they would represent permissive sites to insert foreign peptides and create antigenized Igs expressing selected determinants. Taking advantage of these properties and the fact that Igs are self and long-lived molecules, we expressed a CTL and a helper epitope of influenza virus nucleoprotein and hemagglutinin respectively, within the heavy chain CDR3 loop of an anti-arsonate antibody. We found that foreign peptides comprised of 11 to 15 amino acid residues can be expressed within the V region of the heavy chain without alteration of pairing with the light chain. More striking, the cellular processing machinery is able to generate the peptides from the Ig context which were then recognized by specific T cells. Furthermore, the engineered Igs are able to induce T cell responses specific for the inserted peptide and for influenza virus.The use of engineered Ig molecules as vehicles for T and B cell peptides might represent a valuable strategy to generate safe, long lived reagents able to stimulate strong specific immune responses. This would then overcome the short half life of synthetic peptides based vaccines and the side effects seen in case of recombinant viral proteins or inactivated viruses based vaccines.
ISSN:0883-0185
DOI:10.3109/08830189309061701
出版商:Taylor&Francis
年代:1993
数据来源: Taylor
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15. |
Chimeric T Cell Receptor-Immunoglobulin Molecules: Function and Applications |
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International Reviews of Immunology,
Volume 10,
Issue 2-3,
1993,
Page 279-290
HedrickStephen M.,
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摘要:
The antigen-specific receptors on T and B cells are related by sequence similarities, mechanisms for the generation of diversity, and a common protein domain structure. In contrast, the form of antigen recognition for T- and B-cell antigen receptors is entirely different. Whereas the B cell antigen receptor,i.e., membrane-bound immunoglobulin (Ig), has the potential to recognize a vast diversity of chemical determinants, the T cell antigen receptor (TCR) invariably recognizes oligomeric peptides bound to major histocompatibility complex molecules. A question is whether the variable domains of the TCR and Ig are similar in structure, and if so, can they be substituted one for the other. Recent experiments show that, in some combinations, the variable region of Ig can substitute for the variable region of a TCR, and convey, to a reactive T lymphocyte, the antigen specificity of an Ig molecule. This type of receptor engineering may have interesting applications in disease therapy.
ISSN:0883-0185
DOI:10.3109/08830189309061702
出版商:Taylor&Francis
年代:1993
数据来源: Taylor
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16. |
Preface |
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International Reviews of Immunology,
Volume 10,
Issue 2-3,
1993,
Page -
ZanettiMaurizio,
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PDF (35KB)
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ISSN:0883-0185
DOI:10.3109/08830189309061687
出版商:Taylor&Francis
年代:1993
数据来源: Taylor
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