scholarly journals David vs. Goliath: The Structure, Function, and Clinical Prospects of Antibody Fragments

Antibodies ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 28 ◽  
Author(s):  
Adam Bates ◽  
Christine A. Power
Keyword(s):  
Monoclonal Antibodies ◽  
Lower Cost ◽  
Biological Effects ◽  
Antibody Therapy ◽  
Antibody Fragments ◽  
Intracellular Targeting ◽  
Fast Pace ◽  
Binding Antibody ◽  
Multifunctional Molecules ◽  
Potential Use

Since the licensing of the first monoclonal antibody therapy in 1986, monoclonal antibodies have become the largest class of biopharmaceuticals with over 80 antibodies currently approved for a variety of disease indications. The development of smaller, antigen binding antibody fragments, derived from conventional antibodies or produced recombinantly, has been growing at a fast pace. Antibody fragments can be used on their own or linked to other molecules to generate numerous possibilities for bispecific, multi-specific, multimeric, or multifunctional molecules, and to achieve a variety of biological effects. They offer several advantages over full-length monoclonal antibodies, particularly a lower cost of goods, and because of their small size they can penetrate tissues, access challenging epitopes, and have potentially reduced immunogenicity. In this review, we will discuss the structure, production, and mechanism of action of EMA/FDA-approved fragments and of those in clinical and pre-clinical development. We will also discuss current topics of interest surrounding the potential use of antibody fragments for intracellular targeting and blood–brain barrier (BBB) penetration.

Antibody Therapy for the Control of Viral Diseases: An Update

2019 ◽  
Vol 20 (13) ◽  
pp. 1108-1121 ◽  
Author(s):  
Miriam Dibo ◽  
Eduardo C. Battocchio ◽  
Lucas M. dos Santos Souza ◽  
Matheus D. Veloso da Silva ◽  
Bruna K. Banin-Hirata ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Viral Antigen ◽  
Viral Infections ◽  
Antibody Therapy ◽  
Therapeutic Strategies ◽  
Viral Diseases ◽  
Specific Antibodies ◽  
The Status ◽  
Epidemiological Impact

The epidemiological impact of viral diseases, combined with the emergence and reemergence of some viruses, and the difficulties in identifying effective therapies, have encouraged several studies to develop new therapeutic strategies for viral infections. In this context, the use of immunotherapy for the treatment of viral diseases is increasing. One of the strategies of immunotherapy is the use of antibodies, particularly the monoclonal antibodies (mAbs) and multi-specific antibodies, which bind directly to the viral antigen and bring about activation of the immune system. With current advancements in science and technology, several such antibodies are being tested, and some are already approved and are undergoing clinical trials. The present work aims to review the status of mAb development for the treatment of viral diseases.

scholarly journals Effective use of monoclonal antibodies for treatment of persistent COVID-19 infection in a patient on rituximab

2021 ◽  
Vol 14 (8) ◽  
pp. e243469
Author(s):  
Carlos X Rabascall ◽  
Becky X Lou ◽  
Brianne Navetta-Modrov ◽  
Stella S Hahn
Keyword(s):  
Monoclonal Antibodies ◽  
Symptom Onset ◽  
Severe Disease ◽  
Therapeutic Window ◽  
Immunosuppressed Patient ◽  
Unique Case ◽  
Risk Of Progression ◽  
Immunosuppressed Patients ◽  
Effective Use ◽  
Potential Use

As we are over a year into the COVID-19 pandemic, we have made many forward strides in therapeutics. These treatments, such as monoclonal antibodies, have help mitigate the detrimental and often fatal consequences of COVID-19. The current indication for the use of monoclonal antibodies is mild to moderate COVID-19 infection within 10 days of symptom onset in those who are at high risk of progression to severe disease. However, their role in patients with prolonged symptoms is not clear. We present a unique case of monoclonal antibodies use after 54 days of symptom onset in an immunosuppressed patient with persistent COVID-19 infection despite standard treatment. This case illustrates the potential use of monoclonal antibodies outside of the current recommended therapeutic window in immunosuppressed patients, who may have difficulty with viral clearance.

scholarly journals Generation of Monoclonal Antibodies for Sensitive Detection of Pro-Inflammatory Protein S100A9

2021 ◽  
Vol 11 (10) ◽  
pp. 4659
Author(s):  
Eun-Jung Kim ◽  
Gyu-Min Im ◽  
Chang-Soo Lee ◽  
Yun-Gon Kim ◽  
Byoung Joon Ko ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Calcium Binding ◽  
Nucleotide Sequences ◽  
Antibody Fragments ◽  
High Yield ◽  
Antigen Binding ◽  
Hybridoma Cell Culture ◽  
Inflammatory Protein ◽  
Inflammatory Processes ◽  
Yield And Purity

The calcium-binding protein S100A9 regulates inflammatory processes and the immune response. It is overexpressed in a variety of inflammatory and oncologic conditions. In this study, we produced a recombinant human S100A9 (hS100A9) antigen with high yield and purity and used it to generate a hybridoma cell culture-based monoclonal anti-hS100A9 antibody. We selected five anti-hS100A9 antibodies from cell supernatants that showed high antigen binding efficiency and identified the nucleotide sequences of three antibodies: two with high effective concentration values and one with the lowest value. The antigen and antibody development procedures described herein are useful for producing large amounts of monoclonal antibodies against hS100A9 and other antigens of interest. The nucleotide sequences of the anti-hS100A9 monoclonal antibody revealed herein will be helpful in the generation of recombinant antibodies or antibody fragments against hS100A9.

scholarly journals Therapeutic Application of Monoclonal Antibodies in Pancreatic Cancer: Advances, Challenges and Future Opportunities

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1781
Author(s):  
Gustavo A. Arias-Pinilla ◽  
Helmout Modjtahedi
Keyword(s):  
Pancreatic Cancer ◽  
Monoclonal Antibodies ◽  
Antibody Therapy ◽  
Therapeutic Targets ◽  
Poor Response ◽  
Therapeutic Agents ◽  
Therapeutic Interventions ◽  
Western World ◽  
Wide Range ◽  
Novel Therapeutic

Pancreatic cancer remains as one of the most aggressive cancer types. In the absence of reliable biomarkers for its early detection and more effective therapeutic interventions, pancreatic cancer is projected to become the second leading cause of cancer death in the Western world in the next decade. Therefore, it is essential to discover novel therapeutic targets and to develop more effective and pancreatic cancer-specific therapeutic agents. To date, 45 monoclonal antibodies (mAbs) have been approved for the treatment of patients with a wide range of cancers; however, none has yet been approved for pancreatic cancer. In this comprehensive review, we discuss the FDA approved anticancer mAb-based drugs, the results of preclinical studies and clinical trials with mAbs in pancreatic cancer and the factors contributing to the poor response to antibody therapy (e.g. tumour heterogeneity, desmoplastic stroma). MAb technology is an excellent tool for studying the complex biology of pancreatic cancer, to discover novel therapeutic targets and to develop various forms of antibody-based therapeutic agents and companion diagnostic tests for the selection of patients who are more likely to benefit from such therapy. These should result in the approval and routine use of antibody-based agents for the treatment of pancreatic cancer patients in the future.

scholarly journals Monoclonal antibodies specific to a Ca2+-bound form of lipocortin I distinguish its Ca2+-dependent phospholipid-binding ability from its ability to inhibit phospholipase A2

1990 ◽  
Vol 269 (3) ◽  
pp. 709-715 ◽  
Author(s):  
H Hayashi ◽  
M K Owada ◽  
S Sonobe ◽  
K Domae ◽  
T Yamanouchi ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Phospholipase A2 ◽  
Inhibitory Activity ◽  
Biological Effects ◽  
Free Form ◽  
E Coli ◽  
Phospholipid Binding ◽  
Ef Hand

Lipocortin I, a Ca2(+)-and phospholipid-binding protein without EF-hand structures, has many biological effects in vitro. Its actual role in vivo, however is unknown. We obtained and characterized five monoclonal antibodies to lipocortin I. Two of these monoclonal antibodies (L2 and L4-MAbs) reacted with the Ca(+)-bound form of lipocortin I, but not with the Ca2(+)-free form, both in vivo and in vitro. Lipocortin I required greater than or equal to 10 microM-Ca2+ to bind the two antibodies, and this Ca2+ requirement was not affected by phosphatidylserine. L2-MAb abolished the phospholipase A2 inhibitory activity of lipocortin I and inhibited its binding to Escherichia coli membranes and to phosphatidylserine in vitro. L4-MAb abolished the phospholipase A2 inhibitory activity of lipocortin I, but did not affect its binding to E. coli membranes or to phosphatidylserine. These findings indicated that the inhibition of phospholipase A2 by lipocortin I was not simply due to removal or capping of the substrates in E. coli membranes. Furthermore, an immunofluorescence study using L2-MAb showed the actual existence of Ca2(+)-bound form of lipocortin I in vivo.

scholarly journals The variability of nitro group-protein interaction in the 2,4-dinitrophenyl-binding antibodies M315, M460 and X25 investigated by resonance Raman spectroscopy

1981 ◽  
Vol 197 (1) ◽  
pp. 119-125 ◽  
Author(s):  
P Gettins ◽  
R A Dwek ◽  
R N Perutz
Keyword(s):  
Raman Spectroscopy ◽  
Nitro Group ◽  
Resonance Raman Spectroscopy ◽  
Specific Interaction ◽  
Resonance Raman ◽  
Antibody Fragments ◽  
Antibody Specificity ◽  
Group Protein ◽  
Binding Antibody ◽  
Induced Changes

Pre-resonance Raman spectroscopy was used to study the interactions of the nitro groups of dinitrophenyl haptens with three dinitrophenyl-binding antibody fragments: M315 Fv, M460 Fab‘ and X25 Fab’. The observed changes in frequency of modes associated with the nitro moieties are compared with solvent-induced changes for the model hapten 2,4-dinitroaniline. These comparisons demonstrate a specific interaction via the H2N-C-C-2-NO2 and 4-NO2 groups with the protein. The interaction with the 4-NO2 group appears to be absent for epsilon-N-2,4-dinitrophenyl-L-lysine bound to M315 Fv fragment in contrast with either 2,4-dinitrophenylaspartate or 2,4-dinitrophenylglycine bound to M315 Fv fragment, despite the much tighter binding of the lysine derivative. The implications of this for M315 Fv fragment in terms of the antibody specificity are discussed. Comparisons of the effect of binding to M460 Fab‘ and X25 Fab’ fragments also revealed significant differences in the shifts of the nitro group vibrations of 2,4-dinitrophenyl-lysine and 2,4-dinitroaniline.

The role of isozyme studies in molecular systematics

1990 ◽  
Vol 3 (1) ◽  
pp. 39 ◽  
Author(s):  
AHD Brown
Keyword(s):  
Dna Sequences ◽  
Lower Cost ◽  
Molecular Techniques ◽  
Sampling Strategies ◽  
Recent Emergence ◽  
Local Differentiation ◽  
System Migration ◽  
Potential Use

The recent emergence of molecular techniques for obtaining evidence from DNA sequences to use in systematic studies raises the question of whether the isozyme approach is now superseded. When should the experimental taxonomist spend the limited research dollar on isozymes and when on DNA techniques? The clearest advantages of the latter are the fundamental quality of the data (being directly at the DNA level), and their potential use at all levels of the taxonomic hierarchy. The relative advantages of isozyme techniques are their lower cost, ease and rapidity. Isozymes are most suited to addressing questions at the level of populations, subspecies and species, and only of limited use at higher levels. Yet it is precisely the species level where the systematist is often seeking a variety of evidence to support taxonomic concepts. The capacity to handle a large number of samples, in a directly comparative fashion, means that isozymes are ideal for studying microevolutionary processes such as mating system, migration, local differentiation and hybridisation. These processes act on all kinds of variation, and knowing about them will assist a taxonomist's approach to other levels of evidence. Finally isozyme analysis is useful in the design of sampling strategies and the choice of samples for in-depth molecular analysis. These points are illustrated by a study of variation in Glycine canescens and polyploid origins within the G. tomentella complex, and of partial cleistogamy in G. argyrea.

scholarly journals Monoclonal antibodies directed against the flagella ofCampylobacter jejuni: cross-reacting and serotypic specificity and potential use in diagnosis

1986 ◽  
Vol 96 (3) ◽  
pp. 377-384 ◽  
Author(s):  
D. G. Newell
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Campylobacter Jejuni ◽  
Clinical Material ◽  
Faecal Material ◽  
Ofcampylobacter Jejuni ◽  
Elisa Technique ◽  
Flagellar Antigen ◽  
Potential Use

SUMMARYNine monoclonal antibodies directed against the flagella ofCampylobacter jejunistrain 81116 have been investigated for serotypic and cross-reacting activity using a panel of 17 Penner serotype strains ofC. jejuni.Four monoclonal antibodies were exclusively specific for serotype-6 strains, which was the serotype ofC. jejunistrain 81116. Two monoclonal antibodies cross-reacted with all the flagellated strains ofC jejunitested. One of these cross-reacting monoclonal antibodies, CF5, was found to react with all otherCampylobacterspecies exceptC. sputorum bulbulusbut it did not react with other bacterial entcropathogens. An antigencapture ELISA technique was established, using this monoclonal antibody, which could detect flagellar antigen in human faecal material. These anti-flagella monoclonal antibodies therefore may be valuable in the diagnosis and serotyping ofC. jejuniin clinical material.

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