-
Human Cell Jul 2021Ovarian cancer is the most deadly gynecological malignant tumor in the world today. Previous studies have shown that insulin-like growth factor-1 receptor (IGF-1R) is...
Ovarian cancer is the most deadly gynecological malignant tumor in the world today. Previous studies have shown that insulin-like growth factor-1 receptor (IGF-1R) is closely related to the occurrence and development of ovarian cancer, and ovarian cancer cells endogenously express high IGF-1R. Therefore, IGF-1R could be used as a target for ovarian cancer treatment. In the past, the strategy for preparing IGF-1R antagonists was to use IGF-1R antibody and small-molecule inhibitor. In the current research, we use a new method to prepare IGF-1R antagonists. We prepared a series of IGF-1 internal imaging anti-idiotypic antibodies by anti-idiotypic antibody strategy. After a series of screening and identification, one of the anti-idiotypic antibodies (B003-2A) was selected for further evaluation, and the results showed that B003-2A could not only inhibit the binding of IGF-1 to IGF-1R but also inhibit the signaling mediated by IGF-1R. Further work showed that B003-2A inhibited the proliferation of ovarian cancer cells in vivo and in vitro. In addition, the current study also indicates that B003-2A could enhance the sensitivity of cisplatin in cisplatin-resistant ovarian cancer cell lines. In summary, our research shows that B003-2A can be used to treat ovarian cancer. The current study also laid the foundation for the development of IGF-1R antagonist.
Topics: Animals; Antibodies, Anti-Idiotypic; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Cisplatin; Drug Resistance, Neoplasm; Female; Gene Expression; Humans; Insulin-Like Growth Factor I; Mice, Inbred BALB C; Ovarian Neoplasms; Rabbits; Receptor, IGF Type 1; Mice
PubMed: 33905103
DOI: 10.1007/s13577-021-00535-x -
Bioanalysis Aug 2023MK-1654 is a fully human monoclonal antibody with YTE mutations currently in phase III clinical trials for prophylactic use in protecting infants from human...
MK-1654 is a fully human monoclonal antibody with YTE mutations currently in phase III clinical trials for prophylactic use in protecting infants from human respiratory syncytial virus infection. We generated anti-idiotype (anti-ID) and anti-YTE antibodies against MK-1654 by panning with MorphoSys HuCal phage libraries, and used the antibodies in the development of MK-1654 pharmacokinetic (PK) and immune response (IR) assays. Detection of MK-1654 in nonhuman primate and human nasal wash samples showed combined use of anti-ID and anti-YTE antibodies can deliver desired sensitivity and accuracy in PK studies. IR studies showed anti-ID can serve as suitable positive control in neutralizing antibody assays. Phage-derived anti-IDs and anti-YTEs are suitable for PK and IR assays.
Topics: Animals; Humans; Bacteriophages; Antibodies, Neutralizing; Antibodies, Monoclonal; Immunity
PubMed: 37515532
DOI: 10.4155/bio-2023-0081 -
Journal of Agricultural and Food... Oct 2021Mycotoxins are toxic contaminants in foods and feeds that are naturally occurring and largely unavoidable. Determining their contents in these products is essential to... (Review)
Review
Mycotoxins are toxic contaminants in foods and feeds that are naturally occurring and largely unavoidable. Determining their contents in these products is essential to protect humans from harm. Immunoassays of mycotoxins have been well-established because they are fast, sensitive, simple, and cost-effective. However, a major limitation of immunoassays is the requirement of toxic mycotoxins as competing antigens, standards, or competing tracers. Mimotopes are peptides or proteins that can specifically bind to antibodies and compete with analytes for binding sites by mimicking antigenic epitopes. They can be employed as substitutes for competing antigens, standards, or competing tracers to avoid use of mycotoxins. This review summarizes the production and functionalization of the two main kinds of mimotopes, mimic peptides and anti-idiotypic antibodies (Ab2), and their applications in rapid analysis of mycotoxins.
Topics: Antigens; Epitopes; Humans; Immunoassay; Mycotoxins; Peptides
PubMed: 34583509
DOI: 10.1021/acs.jafc.1c04169 -
Rhinology Apr 2021The majority of patients with uncontrolled severe CRSwNP, asthma and atopic dermatitis share a similar T helper 2 type inflammation linked to their underlying phenotype.... (Review)
Review
BACKGROUND
The majority of patients with uncontrolled severe CRSwNP, asthma and atopic dermatitis share a similar T helper 2 type inflammation linked to their underlying phenotype. This discovery has triggered new research around treatments targeting specific cytokines driving inflammation in CRSwNP like IL-4, IL-13, IL-5 and IgE. Biologicals are increasingly tested as additional tre- atment for patients suffering from severe chronic rhinosinusitis with nasal polyps (CRSwNP). Their efficacy has been demonstrated in multiple studies. All studies differ in terms of baseline characteristics of included patients and outcome parameters analysed.
AIMS
A comparative analysis of the efficacy of reported biologicals for CRSwNP based on the published data for phase 2 and 3 studies. The aim was to provide a comprehensive overview across the different biologicals and outcome parameters.
METHODS
In a first step we critically selected out of all available phase 2 and 3 clinical trials the ones containing the most rigorous and compatible study designs. Meaning studies that comply with a need for a clear definition of CRSwNP, at least two administra- tion doses, comparable timeframes and the same outcome parameters studied. This assessment was performed using a PRISMA search. We retained 7 studies with significant data for dupilumab, mepolizumab and omalizumab. In a second step the effect-sizes of treatment with those biologicals were compared for the most important outcome parameters both patient relevant (nasal con- gestion, smell loss and SNOT-22 scores) and patient irrelevant (CT scan Lund-Mackay, smell test and nasal polyp scores). Therapy duration of 16 to 25 weeks was chosen for evaluation of efficacy.
RESULTS
A direct comparison of efficacy between dupilumab, mepolizumab and omalizumab is challenging given differences in inclusion criteria, outcome parameters and time-points of analyses. We have been able to conclude that effect sizes of dupilumab, mepolizumab and omalizumab seem large enough to reflect a major reduction in symptom burden as experienced by patients suffering from refractory CRSwNP. The effect size of dupilumab on both patient relevant and patient irrelevant parameters of smell loss are clearly significant and reflect the clinical experience of major reduction of smell impairment in treated patients.
CONCLUSION
Despite the heterogeneity of protocols, dosages and time-points of analyses of biological trials in CRSwNP, this over- view highlights outcomes of biological treatment in CRSwNP in a comprehensive way. Real-life registries, comparative trials and/ or endotype-driven treatment plans are needed to provide the answers to the multiple questions that are still open today.
Topics: Chronic Disease; Humans; Nasal Polyps; Omalizumab; Rhinitis; Sinusitis
PubMed: 33459728
DOI: 10.4193/Rhin20.570 -
The New England Journal of Medicine Mar 2022
Topics: Antibodies, Anti-Idiotypic; Antibodies, Neutralizing; COVID-19; Humans; SARS-CoV-2; Vaccination
PubMed: 35108466
DOI: 10.1056/NEJMc2119443 -
The New England Journal of Medicine Mar 2022
Topics: Antibodies, Anti-Idiotypic; Antibodies, Neutralizing; COVID-19; Humans; SARS-CoV-2; Vaccination
PubMed: 35108467
DOI: 10.1056/NEJMc2119443 -
Respiratory Investigation Jul 2021Asthma is considered a syndrome composed of heterogeneous disorders involving complex chronic airway inflammation. Patients with severe asthma, prolonged symptoms, and... (Review)
Review
Asthma is considered a syndrome composed of heterogeneous disorders involving complex chronic airway inflammation. Patients with severe asthma, prolonged symptoms, and frequent asthma exacerbations, despite high doses of inhaled corticosteroids, may benefit from treatment with biologics. Four types of biologics are available for severe asthma, including an anti-immunoglobulin E (IgE) antibody (omalizumab), anti-interleukin (IL)-5 antibody (mepolizumab and reslizumab), anti-IL-5 receptor α antibody (benralizumab), and anti-IL-4 receptor α antibody (dupilumab). Biologics for patients with severe asthma demonstrate high therapeutic efficacy and provide significant clinical benefits, including the prevention of asthma exacerbations, alleviation of symptoms, improvement in the quality of life and respiratory function, and reduction in frequencies of hospitalization and emergency outpatient visits. This review provides an overview of the modulation of immunological features by each of the four established biologics in patients with severe allergic asthma. Given the extensive immunomodulatory effects of biologics, further analyses of their precise effects on the human immune system are warranted.
Topics: Anti-Asthmatic Agents; Asthma; Biological Products; Humans; Omalizumab; Quality of Life
PubMed: 33893067
DOI: 10.1016/j.resinv.2021.03.003 -
Current Opinion in Allergy and Clinical... Jun 2021To familiarize the reader with the most recent insights in the use of Omalizumab (monoclonal anti-immunoglobulin E) monotherapy in the treatment of patients with severe... (Review)
Review
PURPOSE OF REVIEW
To familiarize the reader with the most recent insights in the use of Omalizumab (monoclonal anti-immunoglobulin E) monotherapy in the treatment of patients with severe food allergy.
RECENT FINDINGS
The current data from early stage clinical trials show that Omalizumab may be safe and effective by itself in providing desensitization to one or several foods without requiring allergen exposure.
SUMMARY
In the near future, advances in knowledge will guide the adoption and implementation of any new therapy for food allergy and allow the development of a personalized treatment tailored on the specific patient's profile.
Topics: Allergens; Antibodies, Monoclonal; Food Hypersensitivity; Humans; Immunoglobulin E; Omalizumab
PubMed: 33769312
DOI: 10.1097/ACI.0000000000000744 -
Frontiers in Immunology 2022Urticaria is a symptom of acute skin allergies that is not clearly understood, but mast cell histamine is hypothesized to cause swelling and itching. Omalizumab, an... (Review)
Review
Urticaria is a symptom of acute skin allergies that is not clearly understood, but mast cell histamine is hypothesized to cause swelling and itching. Omalizumab, an anti-human IgE antibody that traps IgE and prevents its binding to high-affinity IgE receptors, is effective in treating urticaria. We recently experienced a case of urticaria refractory to antihistamine therapy in which the peripheral-blood basophil count responded to omalizumab therapy and its withdrawal. Furthermore, the peripheral-blood basophils showed an unexpected increase in the expression of a cell surface activation marker. This phenomenon has been reported by other analyses of basophil and mast cell dynamics during omalizumab treatment. Here, we analyze these observations and formulate a hypothesis for the role of basophils in urticaria. Specifically, that activated basophils migrate to the local skin area, lowering peripheral-blood counts, omalizumab therapy alters basophilic activity and causes their stay in the peripheral blood. We hope that our analysis will focus urticaria research on basophils and reveal new aspects of its pathogenesis.
Topics: Anti-Allergic Agents; Basophils; Humans; Immunoglobulin E; Omalizumab; Urticaria
PubMed: 35663949
DOI: 10.3389/fimmu.2022.883692 -
Methods in Molecular Biology (Clifton,... 2020The antibody repertoire of cartilaginous fish comprises an additional heavy-chain-only antibody isotype that is referred to as IgNAR (immunoglobulin novel antigen...
The antibody repertoire of cartilaginous fish comprises an additional heavy-chain-only antibody isotype that is referred to as IgNAR (immunoglobulin novel antigen receptor). Its antigen-binding site consists of one single domain (vNAR) that is reportedly able to engage a respective antigen with affinities similar to those achieved by conventional antibodies. While vNAR domains offer a reduced size, which is often favorable for applications in a therapeutic as well as a biotechnological setup, they also exhibit a high physicochemical stability. Together with their ability to target difficult-to-address antigens such as virus particles or toxins, these shark-derived antibody domains seem to be predestined as tools for biotechnological and diagnostic applications. In the following chapter, we will describe the isolation of anti-idiotypic vNAR domains targeting monoclonal antibody paratopes from semi-synthetic, yeast-displayed libraries. Anti-idiotypic vNAR variants could be employed for the characterization of antibody-based therapeutics (such as antibody-drug conjugates) or as positive controls in immunogenicity assays. Peculiarly, when using semi-synthetic vNAR libraries, we found that it is not necessary to deplete the libraries using unrelated antibody targets, which enables a fast and facile screening procedure that exclusively delivers anti-idiotypic binders.
Topics: Animals; Antibodies, Anti-Idiotypic; Fish Proteins; Peptide Library; Protein Domains; Sharks; Single-Chain Antibodies
PubMed: 31625097
DOI: 10.1007/978-1-4939-9853-1_11