Use Of Human Monoclonal Antibodies Research Articles

USE OF MONOCLONAL ANTIBODIES TO HUMAN CYTOKINES IN DIAGNOSTIC AND ANALYTICAL STUDIES

The use of human monoclonal antibodies in diagnostics and analytical studies is determined by the rapid development of technologies and approaches in the field of immunology and clinical laboratory diagnostics. Cytokines, as biologically active substances, play a key role in the regulation of immunity, inflammation and other physiological processes. The use of monoclonal antibodies to cytokines provides an opportunity to accurately determine their concentration and study the interaction with other molecules in clinical studies. The development of new diagnostic methods and analytical studies using monoclonal antibodies opened up prospects for increasing the accuracy and sensitivity of the determination of various diseases. This is especially important in the context of medicine, where accurate diagnosis becomes fundamental for choosing the optimal method. Aim. The purpose of this work was to analyze the possibilities and advantages of using monoclonal antibodies to human cytokines in diagnostics and analytical studies, in particular their use in immunological biosensors, for monitoring the immunological status of patients after organ transplantation and diagnosing oncological diseases. Methods. A comprehensive review of literature was conducted, encompassing multiple databases including Medline (PubMed), Web of Science, Scopus, Google Scholar and other relevant sources up to the year 2024. Keywords employed in the search included biosensors, cell markers, monoclonal antibodies, leukemia and Western blotting, transplantation. Results. The paper investigated the potential and advantages of using human monoclonal antibodies to cytokines in medical diagnostics and analytical research. Their application in biosensors for precise determination of cytokine concentrations, immunophenotyping of blood cells and tissues, diagnosing tumors of various histogenesis, treating leukemias and lymphomas, determining immunological status and composition of the immune system cells were analyzed. The methodology of comprehensive immunological examination after organ transplantation and treatment, including аcquired immunodeficiency syndrome (AIDS), was also considered. Conclusions. Monoclonal antibodies, effective in biosensors, are used in various fields such as biological research, clinical diagnostics, and environmental monitoring. Their use has limitations, such as cost, complexity of acquisition, and potential loss of signal sensitivity. Immunophenotyping allows the identification of blood cells based on their markers, which is important for hematological diagnostics. Immunohistochemical tissue studies use monoclonal antibodies to verify tumors and detect infectious diseases. Diagnosis of leukemias and lymphomas using monoclonal antibodies helps to determine tumor type and optimal treatment. Western blotting is used to determine proteins in tissues or blood, including confirming diseases such as Lyme disease or Human immunodeficiency virus (HIV infection. Flow cytometry, enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction (PCR) are also used in immunological laboratories for disease diagnosis and immune status assessment.

Clinical observation of pneumomediastinum in a case of severe COVID-19-associated pneumonia in a teenager

Aim. Demonstration of the clinical case of pneumomediastinum in a teenager with severe COVID-19- associated pneumonia.Materials and methods. The clinical case of spontaneous pneumomediastinum was presented, which was a complication of the severe course of COVID-19 pneumonia in a teenager.Results. Patient Ch., 15 years old, with obesity of the 1st degree, was admitted to the hospital of infectious diseases for patients with a COVID-19 on the 7th day of the illness in a severe condition and had complaints of an increase in body temperature to 40ºC, pronounced cough and weakness, dyspnea when walking and at rest. The PCR test for SARS-CoV-2 gave a positive result. Multispiral computed tomography showed polysegmental interstitial lesion of both lungs, which had multiple areas of “ground glass”, signs of pneumomediastinum, subcutaneous emphysema of the upper third of the chest, left-sided pleural effusion. The volume of lung tissue lesion was 50% on the right and 85% on the left. The positive effect of treatment was not observed after 2-3 days in the hospital. The condition of heavy severity continued due to intoxication syndrome, respiratory failure, inflammatory changes in lung tissue syndrome. In this regard, the patient was injected intravenously with tocilizumab (Actemra®) 400 mg. The child was released on the 20th day of hospitalization with a positive clinical effect.Conclusion. The above clinical case demonstrates that in children a novel coronavirus infection can occur not only in severe form, but also with the possible development of complications in the form of pneumomediastinum and low effectiveness of antibacterial and antiviral therapy, which required the use of humanized monoclonal antibodies (tocilizumab).

Modern Immunotherapy in the Treatment of Triple-Negative Breast Cancer.

Simple SummaryThis review summarizes reports from the latest clinical trials assessing the safety and clinical effectiveness of new biological drugs stimulating the immune system to fight cancer. The aim of this study is to show the enormous therapeutic potential of monoclonal antibodies in the treatment of cancer, in particular triple negative breast cancer (TNBC). Introduction of these innovative drugs to the standard clinical cancer therapies, including TNBC, allows for an increase in the response rate to the applied treatment, and consequently extending the lives of patients suffering from cancer. We hope to draw attention to the extremely difficult-to-treat TNBC, as well as the importance of the development of clinical trials evaluating drugs modulating the immune system in TNBC therapy.Triple-Negative Breast Cancer is a subtype of breast cancer characterized by the lack of expression of estrogen receptors, progesterone receptors, as well as human epidermal growth factor receptor 2. This cancer accounts for 15–20% of all breast cancers and is especially common in patients under 40 years of age, as well as with the occurring BRCA1 mutation. Its poor prognosis is reflected in the statistical life expectancy of 8–15 months after diagnosis of metastatic TNBC. So far, the lack of targeted therapy has narrowed therapeutic possibilities to classic chemotherapy. The idea behind the use of humanized monoclonal antibodies, as inhibitors of immunosuppressive checkpoints used by the tumor to escape from immune system control, is to reduce immunotolerance and direct an intensified anti-tumor immune response. An abundance of recent studies has provided numerous pieces of evidence about the safety and clinical benefits of immunotherapy using humanized monoclonal antibodies in the fight against many types of cancer, including TNBC. In particular, phase three clinical trials, such as the IMpassion 130, the KEYNOTE-355 and the KEYNOTE-522 resulted in the approval of immunotherapeutic agents, such as atezolizumab and pembrolizumab by the US Food and Drug Administration in TNBC therapy. This review aims to present the huge potential of immunotherapy using monoclonal antibodies directed against immunosuppressive checkpoints—such as atezolizumab, avelumab, durvalumab, pembrolizumab, nivolumab, cemiplimab, tremelimumab, ipilimumab—in the fight against difficult to treat TNBCs as monotherapy as well as in more advanced combination strategies.

Major Immunogens Targeted by IgE During Helminth Infection

Much of our understanding of the targets of IgE comes from studies of allergy, though little is known about the natural immunogenic targets seen following parasitic worm infections. The use of human monoclonal antibodies (mAbs) allow for an unbiased, comprehensive characterization of the immunodominant antigens targeted by IgE in conditions (e.g., allergy, helminth infection) associated with elevated levels of IgE.

COVID-19 in patients with psoriasis: A Latin American case series

To the Editor: The impact that COVID-19 has on patients with psoriasis is not completely clear. It has been reported that patients usually experience mild symptoms; however, pneumonia may develop in up to 15% of these patients, and 5% of patients progress to acute respiratory distress syndrome.1 Controversy over the use of human monoclonal antibodies against cytokines (biologics) and other immunomodulatory therapies has increased the interest in the dermatologic community, since it is presumed that these patients may have a greater risk of requiring in-hospital management during acute infection.

The Countermeasure for Zika Virus: A Hard Nut to Be Cracked

The emergence of Zika virus (ZIKV) infection in America has caused a new threat worldwide, as it is linked with the increased incidence of congenital microcephaly in neonates and development of Guillain–Barré syndrome. A number of potential antiviral drugs such as sofosbuvir, BCX4430, NITD008 and 7-DMA have shown activity against ZIKV both in vitro and in vivo. Similarly, different research organizations and academic institutions are trying hard to develop a vaccine against the ZIKV. Some of these groups have received approval from the US FDA to start Phase I clinical trials. Immuno-based treatment strategies, such as use of humanized monoclonal antibodies (hE16 and CR4373) have also entered clinical trials. However, a licensed vaccine is still a long way off and efforts should be made to accelerate the evaluation procedures while minimizing the delay in licensing.

Development of an Extended-Specificity Multiplex Immunoassay for Detection of Streptococcus pneumoniae Serotype-Specific Antigen in Urine by Use of Human Monoclonal Antibodies.

Current pneumococcal vaccines cover the 10 to 23 most common serotypes of the 92 presently described. However, with the increased usage of pneumococcal-serotype-based vaccines, the risk of serotype replacement and an increase in disease caused by nonvaccine serotypes remains. Serotype surveillance of pneumococcal infections relies heavily on culture techniques, which are known to be insensitive, particularly in cases of noninvasive disease. Pneumococcal-serotype-specific urine assays offer an alternative method of serotyping for both invasive and noninvasive disease. However, the assays described previously cover mainly conjugate vaccine serotypes, give little information about circulating nonvaccine serotypes, and are currently available only in one or two specialist laboratories. Our laboratory has developed a Luminex-based extended-range antigen capture assay to detect pneumococcal-serotype-specific antigens in urine samples. The assay targets 24 distinct serotypes/serogroups plus the cell wall polysaccharide (CWP) and some cross-reactive serotypes. We report that the assay is capable of detecting all the targeted serotypes and the CWP at 0.1 ng/ml, while some serotypes are detected at concentrations as low as 0.3 pg/ml. The analytical serotype specificity was determined to be 98.4% using a panel of polysaccharide-negative urine specimens spiked with nonpneumococcal bacterial antigens. We also report clinical sensitivities of 96.2% and specificities of 89.9% established using a panel of urine specimens from patients diagnosed with community-acquired pneumonia or pneumococcal disease. This assay can be extended for testing other clinical samples and has the potential to greatly improve serotype-specific surveillance in the many cases of pneumococcal disease in which a culture is never obtained.

The Experience of Successful Use of Adalimumab in a Patient With Juvenile Arthritis Associated With Enthesitis and Uveitis

The article describes the case of successful use of human monoclonal antibodies to the tumor necrosis factor- adalimumab in a patient with a severe course of juvenile arthritis associated with enthesitis and uveitis resistant to non-steroidal anti-inflammatory drugs, methotrexate, glucocorticosteroids that have been applied topically and retrobulbarly. After the first adalimumab administration, the pain syndrome was stopped, the duration of morning stiffness was significantly reduced, the laboratory indices of the disease activity were normalized by the 4th week of treatment, uveitis activity was stopped, the inflammatory changes in the joints regressed and the phase of inactive disease was ascertained by the 12th week. The duration of remission of articular syndrome and uveitis during treatment with adalimumab was 26 months. Adverse reactions were not registered during therapy.

Population structure of the dengue viruses, Aragua, Venezuela, 2006–2007. Insights into dengue evolution under hyperendemic transmission

During the past three decades there has been a notable increase in dengue disease severity in Venezuela. Nevertheless, the population structure of the viruses being transmitted in this country is not well understood. Here, we present a molecular epidemiological study on dengue viruses (DENV) circulating in Aragua State, Venezuela during 2006–2007. Twenty-one DENV full-length genomes representing all of the four serotypes were amplified and sequenced directly from the serum samples. Notably, only DENV-2 was associated with severe disease. Phylogenetic trees constructed using Bayesian methods indicated that only one genotype was circulating for each serotype. However, extensive viral genetic diversity was found in DENV isolated from the same area during the same period, indicating significant in situ evolution since the introduction of these genotypes. Collectively, the results suggest that the non-structural (NS) proteins may play an important role in DENV evolution, particularly NS1, NS2A and NS4B proteins. The phylogenetic data provide evidence to suggest that multiple introductions of DENV have occurred from the Latin American region into Venezuela and vice versa. The implications of the significant viral genetic diversity generated during hyperendemic transmission, particularly in NS protein are discussed and considered in the context of future development and use of human monoclonal antibodies as antivirals and tetravalent vaccines.

Handbook of Therapeutic Antibodies: Technologies, Emerging Developments and Approved Therapeutics Edited by Professor Stefan Dubel, Wiley-Blackwell. 2009. 1204pp ISBN: 978-3-527-32902-1 http://www.wiley.com/wileyCDA/wileyTitle/productCd-3527329021.html

Handbook of Therapeutic Antibodies: Technologies, Emerging Developments and Approved Therapeutics Edited by Professor Stefan Dubel, Wiley-Blackwell. 2009. 1204pp ISBN: 978-3-527-32902-1 http://www.wiley.com/wileyCDA/wileyTitle/productCd-3527329021.html

Analysis of HER2 gene amplification and protein expression in esophageal squamous cell carcinoma

The HER2 gene, which is located on chromosomes 17, is a therapeutic target for cancer. Amplification of HER2 has been described in several tumor types. However, few studies of HER2 gene amplification and protein expression in esophageal carcinoma have been conducted. This study was to investigate the relationship between the expression of HER2/neu and the clinical characteristics, including survival rate, of esophageal squamous carcinoma. The clinical data of 145 patients admitted in Renmin Hospital of Wuhan University, from 2000 to 2005, were reviewed. The HER2 protein expression and gene status in 145 esophageal carcinomas were evaluated using immunohistochemistry and fluorescence in situ hybridization. The survival rate was calculated by the Kaplan-Meier method and the log-rank test using SPSS13.0 software. Compared to normal esophageal epithelium (23/95, 24.2%), HER2 protein was overexpressed in most esophageal squamous carcinoma tissues (60/145, 41.4%), of which 45 (31.0%) were 2+ and 15 (10.4%) were 3+, HER2 overexpression associated significantly with HER2 gene amplification. There is a correlation between the overexpression of HER2 and the differentiation of the carcinoma, the HER2 gene amplification and the differentiation of the carcinoma and the tumor stage. According to univariate analysis, there was a significant difference in survival rates when cases with and without HER-2/neu overexpression or amplification were compared. HER-2/neu amplification/overexpression may be used as an independent prognostic factor in patients with esophageal squamous cancer, and patients with HER-2/neu amplification/overexpression might be potential candidates for new adjuvant therapies that involve the use of humanized monoclonal antibodies.

Efficacy of Human Monoclonal Antibodies Against H5N1 Influenza

Although currently circulating H5N1 viruses are not efficiently transmitted from person to person, H5N1 influenza remains a major global threat. New treatment strategies are urgently needed. Now, researchers (one of whom is named on a patent relating to the generation and use of human monoclonal antibodies) have generated anti-H5N1 monoclonal antibodies (mAbs) from B-cells of four Vietnamese patients who survived H5N1 infections. They selected …

HER-2/neu overexpression is an independent prognostic factor in colorectal cancer

The HER-2/neu protein is intimately involved with normal cell proliferation and tissue growth, as it is extensively homologous and is related to the epidermal growth factor receptor. This phenomenon has been most intensively studied in the context of breast carcinoma, in which its amplification and overexpression correlate with the overall course of disease and poor prognoses, and also constitute a predictive factor of poor response to chemotherapy and endocrine therapy. In this study, we investigated the relationships between the expression of HER-2/neu and the clinicopathological characteristics of colorectal cancer, including survival. This study was performed with a view toward the future introduction of Herceptin therapy for colorectal cancer patients. HER-2/neu overexpression and gene amplification were examined via semiquantitative standardized immunohistochemical staining and fluorescence in situ hybridization (FISH) in 137 colorectal cancer patients who underwent curative surgery at the Kangbuk Samsung Hospital. Sixty-five (47.4%) out of 137 patients were determined by immunohistochemistry to have overexpressed HER-2/neu protein. HER-2/neu gene amplification was detected in two patients by FISH. Tumors with HER-2/neu overexpression showed higher postoperative recurrence rate (39.3% vs 14.6%, p=0.013). Tumors with HER-2/neu overexpression were associated with poor 3-year (70.8% vs 83.7%) and 5-year survival rates (55.1% vs 78.3%, p<0.05). Advanced TNM stage, postoperative recurrence, and overexpression of HER-2/neu were found to be independently related to survival by multivariate analysis. HER-2/neu overexpression may constitute an independent prognostic factor in colorectal cancer patients, and patients exhibiting HER-2/neu overexpression might constitute potential candidates for a new adjuvant therapy which involves the use of humanized monoclonal antibodies.

HER-2/neu Amplification Is an Independent Prognostic Factor in Gastric Cancer

The HER-2/neu protein is intimately involved with normal cell proliferation and tissue growth and is extensively homologous and related to the epidermal growth factor receptor. HER-2/neu protein expression has been most intensively studied in the context of breast carcinoma, in which its amplification and overexpression correlate with the overall course of disease, and with a poor prognosis, and constitute a predictive factor of poor response to chemotherapy and endocrine therapy. In this study, we investigated the relationship between the expression of HER-2/neu and the clinicopathological characteristics of tumors, including survival. This study was performed with a view toward the future introduction of Herceptin therapy for gastric cancer patients. HER-2/neu overexpression and gene amplification was examined with semiquantitative standardized immunohistochemical staining, chromogenic in situ hybridization (CISH), and fluorescence in situ hybridization (FISH) in 182 gastric cancer patients who underwent curative surgery at the Kangbuk Samsung Hospital. Twenty-nine (15.9%) of 182 patients expressed the HER-2/neu protein by immunohistochemistry. HER-2/neu gene amplification was detected in seven patients by CISH and FISH. Intestinal-type cancers exhibited higher rates of HER-2/neu amplification than did diffuse-type cancers (P < 0.05). Tumors with HER-2/neu amplification were associated with poor mean survival rates (922 vs 3243 days) and 5-year survival rates (21.4% vs 63.0%; P < 0.05). Age, TNM stage, and amplification of HER-2/neu were found to be independently related to survival by multivariate analysis. HER-2/neu amplification may constitute an independent prognostic factor in gastric cancer patients, and patients exhibiting HER-2/neu amplification might constitute potential candidates for new adjuvant therapies which involve the use of humanized monoclonal antibodies.

Characterization of the Opsonic and Protective Activity against Staphylococcus aureus of Fully Human Monoclonal Antibodies Specific for the Bacterial Surface Polysaccharide Poly- N -Acetylglucosamine

Carbohydrate antigens are important targets of the immune system in clearing bacterial pathogens. Although the immune system almost exclusively uses antibodies in response to foreign carbohydrates, there is still much to learn about the role of different epitopes on the carbohydrate as targets of protective immunity. We examined the role of acetyl group-dependent and -independent epitopes on the staphylococcal surface of polysaccharide poly-N-acetylated glucosamine (PNAG) by use of human monoclonal antibodies (MAbs) specific for such epitopes. We utilized hybridoma technology to produce fully human immunoglobulin G2 (IgG2) MAbs from B cells of an individual post-Staphylococcus aureus infection and cloned the antibody variable regions to produce an IgG1 form of each original MAb. Specificity and functionality of the purified MAbs were tested in vitro using enzyme-linked immunosorbent assays, complement deposition, and opsonophagocytic assays. We found that a MAb (MAb F598) that bound the best to nonacetylated or backbone epitopes on PNAG had superior complement deposition and opsonophagocytic activity compared to two MAbs that bound optimally to PNAG that was expressed with a native level (>90%) of N-acetyl groups (MAbs F628 and F630). Protection of mice against lethality due to S. aureus strains Mn8 and Reynolds further showed that the backbone-specific MAb had optimal protective efficacy compared with the acetate-specific MAbs. These results provide evidence for the importance of epitope specificity in inducing the optimal protective antibody response to PNAG and indicate that MAbs to the deacetylated form of PNAG could be immunotherapeutic agents for preventing or treating staphylococcal infections.

Tolerability in patients receiving trastuzumab with or without chemotherapy

One of the major expectations from the use of humanized monoclonal antibodies in cancer therapy has been that of exploiting the specificity and sensitivity of the immune system to achieve selective therapeutic effects devoid of the often severe toxicity caused by chemotherapy. The tolerability of trastuzumab (Herceptin) as it emerged from the trials where the drug was used as a single agent or in combination with chemotherapy largely confirmed that expectation. Adverse events most frequently encountered include mild-to-moderate, transient effects related to administration of the first dose of trastuzumab. The incidence of severe or serious adverse effects attributable to trastuzumab was low. However, the occurrence of cardiac toxicity that was unexpectedly high, especially in patients previously or concomitantly treated with anthracyclines, could not be predicted on the basis of the putative mechanism of action of the antibody. The safety profile of trastuzumab is discussed here with a particular focus on cardiotoxicity and the issues relating to patient management during trastuzumab therapy.

Antibody mediated therapy of minmal residual leukemia: Use of humanized monoclonal antibodies and targeted alpha particles

Antibody mediated therapy of minmal residual leukemia: Use of humanized monoclonal antibodies and targeted alpha particles

Human recombinant anti-Rh(D) monoclonal antibodies: Improvement of biological properties by in vitro class-switch

Therapeutic use of human monoclonal antibodies has so far been hampered by their poor availability. Recent developments in recombinant DNA technologies are expected to fill this gap; the variable and constant sequences of antibodies can be selected independently and then subsequently joined to express whole antibodies. We assessed here the potential of this methodology to obtain novel anti-D antibodies with improved biological characteristics. The sequences coding for heavy and light chains of two anti-Rh(D) monoclonal antibodies (one IgG1 and one IgG3) were isolated and co-expressed into murine myeloma cell P3X63.Ag8.653, either directly (parental antibodies) or after exchange of constant heavy chain sequences (class-switched antibodies). Parental antibodies produced either by transfectomas or by hybridomas behaved similarly in analysis of biochemical, binding and effector properties. Class-switched antibodies displayed altered functional properties over parental antibodies. Of particular interest, one of them showed improved phagocytosis potencies over both parental antibodies. Additionally, these results indicate that functional properties do not always simply reflect the addition of properties of constant and variable parts but that interactions between constant and variable regions may interfere.

Interleukin 8 as a novel target for intervention therapy in acute inflammatory diseases

Aberrant production of interleukin 8 (IL-8) has been shown in various human inflammatory diseases. Recent investigations in animal models using either blocking antibodies against IL-8 or disruption of the gene encoding the IL-8 receptor have revealed the involvement of IL-8 in the recruitment of neutrophils and in neutrophil-associated tissue injury in acute inflammation. These studies suggest that IL-8 is a novel target to alleviate acute inflammation. This review describes the properties of IL-8 and discusses different therapeutic approaches to target IL-8, particularly the use of humanized monoclonal antibodies against IL-8 and inhibition of IL-8 gene transcription.

Antibody redesign by chain shuffling from random combinatorial immunoglobulin libraries.

A number of experiments on the shuffling of heavy and light chains from antibodies of defined specificity for the transition-state analogue hapten nitrophenyl phosphonamidate are described. The experiments report on the promiscuity of heavy and light chains in binding antigen and the feasibility of antibody redesign by this shuffling process. The concepts of incestuous and extraclonal promiscuous association are described. Shuffling opens the possibility of generating panels of antibodies with related specificity but of distinct idiotypic composition that may have significance in the use of human monoclonal antibodies in therapy.