Bispezifische Antikörper: Hoffnungsträger in der Krebsimmuntherapie

AbstractNearly seventy years have passed since the first attempts to fuse the antibodies, „magic bullets“ with exquisite target specificity, into multispecific agents that can connect a targeted cell with an effector immune cell. Such efforts have triggered a plethora of engineering advancements to optimize the antigen engagement. Even the most conserved domains of the antibody molecule have been modified to achieve two unique chains pairing, or with an introduction of novel antigen binding sites.

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Aggregation prone regions in antibody sequences raised against Vibrio cholerae: A bioinformatic approach

Current Bioinformatics ◽

10.2174/1574893615666200106120504 ◽

2020 ◽

Vol 15 ◽

Author(s):

Zakia Akter ◽

Anamul Haque ◽

Md. Sabir Hossain ◽

Firoz Ahmed ◽

Md Asiful Islam

Keyword(s):

Vibrio Cholerae ◽

Binding Sites ◽

Bioinformatic Analysis ◽

Antigen Binding ◽

Short Term ◽

Protein Database ◽

The Stability ◽

Bioinformatic Approach ◽

Self Aggregation ◽

Complementarity Determining Region

Background: Cholera, a diarrheal illness causes millions of deaths worldwide due to large outbreaks. Monoclonal antibody used as therapeutic purposes of cholera are prone to be unstable due to various factors including self-aggregation. Objectives: In this bioinformatic analysis, we identified the aggregation prone regions (APRs) of different immunogens of antibody sequences (i.e., CTB, ZnM-CTB, ZnP-CTB, TcpA-CT-CTB, ZnM-TcpA-CT-CTB, ZnP-TcpA-CT-CTB, ZnM-TcpA, ZnP-TcpA, TcpA-CT-TcpA, ZnM-TcpA-CT-TcpA, ZnP-TcpA-CT-TcpA, Ogawa, Inaba and ZnM-Inaba) raised against Vibrio cholerae. Methods: To determine APRs in antibody sequences that were generated after immunizing Vibrio cholerae immunogens on Mus musculus, a total of 94 sequences were downloaded as FASTA format from a protein database and the algorithms such as Tango, Waltz, PASTA 2.0, and AGGRESCAN were followed to analyze probable APRs in all of the sequences. Results: A remarkably high number of regions in the monoclonal antibodies were identified to be APRs which could explain a cause of instability/short term protection of anticholera vaccine. Conclusion: To increase the stability, it would be interesting to eliminate the APR residues from the therapeutic antibodies in a such way that the antigen binding sites or the complementarity determining region loops involved in antigen recognition are not disrupted.

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Predominant VH genes expressed in innate antibodies are associated with distinctive antigen-binding sites

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.96.5.2262 ◽

1999 ◽

Vol 96 (5) ◽

pp. 2262-2267 ◽

Cited By ~ 34

Author(s):

K. J. Seidl ◽

J. A. Wilshire ◽

J. D. MacKenzie ◽

A. B. Kantor ◽

L. A. Herzenberg ◽

...

Keyword(s):

Binding Sites ◽

Antigen Binding ◽

Vh Genes ◽

Innate Antibodies

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Fibrinolysis: A Primordial System Linked to the Immune Response

International Journal of Molecular Sciences ◽

10.3390/ijms22073406 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3406

Author(s):

Robert L. Medcalf ◽

Charithani B. Keragala

Keyword(s):

Binding Sites ◽

Defense Mechanisms ◽

Immune Cell ◽

Immune Defense ◽

Surface Proteins ◽

Cell Behavior ◽

Phylogenetic Studies ◽

Blood Clots ◽

Lower Vertebrates ◽

Almost All

The fibrinolytic system provides an essential means to remove fibrin deposits and blood clots. The actual protease responsible for this is plasmin, formed from its precursor, plasminogen. Fibrin is heralded as it most renowned substrate but for many years plasmin has been known to cleave many other substrates, and to also activate other proteolytic systems. Recent clinical studies have shown that the promotion of plasmin can lead to an immunosuppressed phenotype, in part via its ability to modulate cytokine expression. Almost all immune cells harbor at least one of a dozen plasminogen receptors that allows plasmin formation on the cell surface that in turn modulates immune cell behavior. Similarly, a multitude of pathogens can also express their own plasminogen activators, or contain surface proteins that provide binding sites host plasminogen. Plasmin formed under these circumstances also empowers these pathogens to modulate host immune defense mechanisms. Phylogenetic studies have revealed that the plasminogen activating system predates the appearance of fibrin, indicating that plasmin did not evolve as a fibrinolytic protease but perhaps has its roots as an immune modifying protease. While its fibrin removing capacity became apparent in lower vertebrates these primitive under-appreciated immune modifying functions still remain and are now becoming more recognised.

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Human Milk sIgA Molecules Contain Various Combinations of Different Antigen-Binding Sites Resulting in a Multiple Binding Specificity of Antibodies and Enzymatic Activities of Abzymes

PLoS ONE ◽

10.1371/journal.pone.0048756 ◽

2012 ◽

Vol 7 (11) ◽

pp. e48756 ◽

Cited By ~ 6

Author(s):

Sergey E. Sedykh ◽

Valentina N. Buneva ◽

Georgy A. Nevinsky

Keyword(s):

Human Milk ◽

Binding Sites ◽

Binding Specificity ◽

Enzymatic Activities ◽

Antigen Binding ◽

Multiple Binding

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Orientation of antigen binding sites in dimeric and trimeric single chain Fv antibody fragments

FEBS Letters ◽

10.1016/s0014-5793(98)00292-0 ◽

1998 ◽

Vol 425 (3) ◽

pp. 479-484 ◽

Cited By ~ 35

Author(s):

Lynne J. Lawrence ◽

Alexander A. Kortt ◽

Peter Iliades ◽

Peter A. Tulloch ◽

Peter J. Hudson

Keyword(s):

Binding Sites ◽

Antibody Fragments ◽

Antigen Binding ◽

Single Chain ◽

Single Chain Fv ◽

Fv Antibody ◽

Single Chain Fv Antibody

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Antigen-binding sites dominate the surface properties of antibodies

Immunotechnology ◽

10.1016/s1380-2933(97)89006-9 ◽

1996 ◽

Vol 2 (4) ◽

pp. 276

Keyword(s):

Surface Properties ◽

Binding Sites ◽

Antigen Binding

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A SCANNING AND TRANSMISSION ELECTRON MICROSCOPE STUDY OF ANTIGEN-BINDING SITES ON ROSETTE-FORMING CELLS

Journal of Experimental Medicine ◽

10.1084/jem.137.2.483 ◽

1973 ◽

Vol 137 (2) ◽

pp. 483-493 ◽

Cited By ~ 21

Author(s):

Fred G. Gudat ◽

W. Villiger

Keyword(s):

Binding Sites ◽

Electron Microscope Study ◽

Red Cells ◽

Antigen Binding ◽

Patchy Distribution ◽

Contact Areas ◽

Lymphocyte Surface ◽

Transmission Electron ◽

Transmission Electron Microscope Study ◽

Immunoglobulin Receptors

The ultrastructure of binding sites in rosette-forming cells of mice after immunization with sheep red cells was studied by means of scanning and transmission electron microscopy. It was found that the red cells were bound to the lymphocyte surface in circumscribed, immunoglobulin-containing areas, consistent with a spotlike or patchy distribution of antigen-binding immunoglobulin receptors. In these contact areas the cell membranes formed a gap of 80 Å (range 75–90 Å) which exhibited electron-opaque bridges at high magnification. These results are discussed in the light of the recent recognition of the formation of immunoglobulin spots on the lymphocyte surface after antigen contact. Morphological details suggest that the same mechanism is operating in rosette formation, possibly including the movement of the contact areas on the lymphocyte membrane.

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