scholarly journals Therapeutic Applications of Monoclonal Antibodies in Urologic-Oncology Management - An Update

2021 ◽  
Author(s):  
Maya Kulshekar ◽  
Shridhar C. Ghagane ◽  
Sridevi I. Puranik ◽  
Rajendra B. Nerli ◽  
Murigendra B. Hiremath
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Hematologic Malignancies ◽  
Treatment Modalities ◽  
Magic Bullet ◽  
Urologic Oncology ◽  
Potential Applications ◽  
Hybridoma Technology ◽  
Cancer Types ◽  
Antibody Design

The idea of utilizing immunotherapy for the treatment of cancers has been appealing to scientists and clinicians for over a several decades. Immunotherapy for cancers encompasses knowledge gained from a wide range of disciplines and has the potential to procure the ‘magic bullet’ for the treatment of cancer. Monoclonal antibody-based treatment of cancer has been recognized as one of the most successful therapeutic strategies for both hematologic malignancies and solid tumours in the last 20 years. The discovery of hybridoma technology in late 1975 and the development of chimeric, humanized, and human antibodies have increased the availability and utility of immunotherapy for the treatment of cancer. Metastatic or recurrent cancer continues to be the bane of the urological oncologist. Despite recent improvements in therapeutic management and outcomes for clinically localized disease overall survival rate in patients with the majority of metastatic and recurrent genitourinary malignancies remains relatively unchanged. By targeting tumours through specific or associated antigens, it is possible to selectively eliminate tumour cells and maintain an acceptable toxicity profile. Therapeutic antibodies that target immune cells are also being developed with the goal of breaking local tolerance and stimulating the patient’s anti-tumor immune response. As with other treatment modalities, immunotherapy is far from perfect and requires additional study to optimize clinical response and overcome therapeutic resistance. Modern advances in the field of immunotherapy hold the promise of providing the clinical urologist/oncologist with new tools to fight urological cancer. However, the literature on monoclonal antibody-based immunotherapy with a particular emphasis on target antigens, monoclonal antibody design and potential applications in the field of urology is limited. Hence, the present chapter focuses on the applications of Immunotherapy using monoclonal antibodies for urologic oncology settings such as prostate, bladder, renal, testicular and penile with a hope to highlight its clinical efficacy and also its mechanisms of action in each of these cancer types.

Therapeutic Monoclonal Antibodies in Clinical Practice against Cancer

2020 ◽  
Vol 20 (16) ◽  
pp. 1895-1907
Author(s):  
Navgeet Kaur ◽  
Anju Goyal ◽  
Rakesh K. Sindhu
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Clinical Practice ◽  
Therapeutic Agent ◽  
Hematologic Malignancies ◽  
Immune Checkpoints ◽  
Malignant Cells ◽  
Main Target ◽  
Therapeutic Monoclonal Antibodies ◽  
Cancerous Cells

The importance of monoclonal antibodies in oncology has increased drastically following the discovery of Milstein and Kohler. Since the first approval of the monoclonal antibody, i.e. Rituximab in 1997 by the FDA, there was a decline in further applications but this number has significantly increased over the last three decades for various therapeutic applications due to the lesser side effects in comparison to the traditional chemotherapy methods. Presently, numerous monoclonal antibodies have been approved and many are in queue for approval as a strong therapeutic agent for treating hematologic malignancies and solid tumors. The main target checkpoints for the monoclonal antibodies against cancer cells include EGFR, VEGF, CD and tyrosine kinase which are overexpressed in malignant cells. Other immune checkpoints like CTLA-4, PD-1 and PD-1 receptors targeted by the recently developed antibodies increase the capability of the immune system in destroying the cancerous cells. Here, in this review, the mechanism of action, uses and target points of the approved mAbs against cancer have been summarized.

scholarly journals Immunotherapy in hematologic malignancies

2019 ◽  
Vol 27 (S2) ◽  
Author(s):  
R.R. Kansara ◽  
C. Speziali
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Checkpoint Inhibitors ◽  
Cytotoxic T Cells ◽  
Hematologic Malignancies ◽  
Immune Checkpoints ◽  
Hematologic Neoplasms

The management of hematologic malignancies has traditionally relied on chemotherapy regimens, many of which are still in use today. However, with advancements in the knowledge of tumour pathophysiology, therapies are continually evolving. Monoclonal antibodies against specific targets on tumour cells are now widely used to treat hematologic malignancies, either in combination with chemotherapy or as single agents. Rituximab, a monoclonal antibody against the CD20 antigen, is a good example of successful monoclonal antibody therapy that has improved outcomes for patients with B cell non-Hodgkin lymphomas. Monoclonal antibodies are now being used against the immune checkpoints that function to inhibit T cell activation and subsequent tumour eradication by those cytotoxic T cells. Such therapies enhance T cell–mediated tumour eradication and are widely successful in treating patients with solid tumours such as malignant melanoma. Now, they are slowly finding their place in the management of hematologic neoplasms. Even though, currently, immune checkpoint inhibitors are used for relapsed or refractory hematologic neoplasms, trials are ongoing to evaluate their role in frontline treatment. Our review focuses on the current use of immunotherapies in various hematologic malignancies.

scholarly journals Monoclonal antibodies that immunoreact with a cation-stimulated plant membrane ATPase

1982 ◽  
Vol 203 (1) ◽  
pp. 51-54 ◽  
Author(s):  
J J C Chin
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Plasma Membrane ◽  
Marker Enzyme ◽  
Membrane Atpase ◽  
Hybridoma Technology ◽  
Membrane Antigens ◽  
Monospecific Antibodies

Hybridoma technology has been used successfully to generate monoclonal-antibody probes against protoplast membrane antigens. Hybridomas secreting monoclonal antibodies that either inhibit or stimulate a putative plasma-membrane marker enzyme, (K+ + Mg2+)-stimulated pH 6.5 ATPase, have been identified and cloned. The specificity of monoclonal-antibody probes on the activity of other phosphate-hydrolysing enzymes has also been examined. The production and identification of monospecific antibodies capable of immunoreacting with particular component proteins in a complex plant membrane mixture highlight the usefulness of hybridoma methodology for the enzymologist, especially since such monoclonal antibodies can be used in the purification of proteins by immunoaffinity techniques.

scholarly journals Development of a novel monoclonal antibody against chitinase-like protein YKL-39 applicable for immunohistochemistry

2019 ◽  
Vol 18 (2) ◽  
pp. 27-31
Author(s):  
A. N. Gratchev ◽  
D. V. Samoilova ◽  
S. N. Kurochkin ◽  
O. V. Kovaleva
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Western Blot ◽  
Full Length ◽  
High Expression ◽  
Secreted Protein ◽  
Hybridoma Technology ◽  
Potential Biomarkers

Introduction. Mammalian chitinase-like proteins are produced in the areas of inflammation and in tumors. Some members of chitinase-like proteins family are studied as potential biomarkers of tumors (glioma, prostate and ovary). YKL-39 also known as chitinase-3-like 2 (CHI3L2) is a secreted protein produced by chondrocytes. Its high expression is also found in synoviocytes, lung heart and macrophages.The aim of this study was the development of highly specific monoclonal antibodies against human YKL-39. Materials and methods. Using recombinant full-length human YKL-39 as immunogen using hybridoma technology we have generated monoclonal antibody 1B2G4, that specifically binds YKL-39 in ELISA.Results and conclusion. Obtained antibody was successfully tested in Western blot, immunocytochemistry, immunofluorescence and immunohistochemistry on FFPE sections. It was shown that the antibody binds the full-length YKL-39 protein and does not interact with other chitinase-like proteins. 

PERSPECTIVES OF APPLICATION OF ANTIBODIES AGAINST ENDOGLIN (CD105) FOR VISUALIZATION AND ANTI-ANGIOGENE THERAPY OF TUMORS

2018 ◽  
Vol 64 (4) ◽  
pp. 504-507
Author(s):  
Vladimir Klimovich ◽  
Natalya Vartanyan ◽  
Anastasiya Stolbovaya ◽  
Lidiya Terekhina ◽  
Olga Shashkova ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Monoclonal Antibodies ◽  
Human Plasma ◽  
Vascular Endothelium ◽  
Immune Complexes ◽  
Targeted Delivery ◽  
Biological Fluids ◽  
Therapeutic Drugs ◽  
Cultured Endothelial Cells ◽  
Hybridoma Technology

During last years monoclonal antibodies (MAB) directed against vascular endothelium markers demonstrated their efficiency for visualization and targeted delivery of therapeutic drugs to tumors. Endoglin (CD105) which serves as a key element that determines endothelial cells quiescence or activation is one of such markers. Endoglin is highly expressed on the vascular endothelium of growing tumors. A first panel of MAB against endoglin in our country was produced at the hybridoma technology laboratory of RRC RST named after A.M. Granov. On the basis of these MAB ELISA was created allowing detection of endoglin in human plasma and other biological fluids. Several MAB had been shown to bind endoglin on the membrane of the cultured endothelial cells and to persist there for several hours. During the first 30 min after binding some of the immune complexes “endoglin-MAB” were internalized into the cytoplasm and were found included in the endosomes. In future these MAB can be used to create the reagents for the addressed delivery of isotope tags both on the membrane and into the cytoplasm of endothelial cells.

Rapid quantification and in situ detection of nitrifying bacteria in biofilms by monoclonal antibody method

2000 ◽  
Vol 41 (4-5) ◽  
pp. 301-308 ◽  
Author(s):  
N. Noda ◽  
H. Ikuta ◽  
Y. Ebie ◽  
A. Hirata ◽  
S. Tsuneda ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Fluorescent Antibody ◽  
Nitrifying Bacteria ◽  
Fluorescent Antibody Technique ◽  
Antibody Technique ◽  
Antibody Method ◽  
In Situ Detection ◽  
Rapid Quantification

Fluorescent antibody technique by the monoclonal antibody method is very useful and helpful for the rapid quantification and in situ detection of the specific bacteria like nitrifiers in a mixed baxterial habitat such as a biofilm. In this study, twelve monoclonal antibodies against Nitrosomonas europaea (IFO14298) and sixteen against Nitrobacter winogradskyi (IFO14297) were raised from splenocytes of mice (BALB/c). It was found that these antibodies exhibited little cross reactivity against various kinds of heterotrophic bacteria. The direct cell count method using monoclonal antibodies could exactly detect and rapidly quantify N. europaea and N. winogradskyi. Moreover, the distribution of N. europaea and N. winogradskyi in a biofilm could be examined by in situ fluorescent antibody technique. It was shown that most of N. winogradskyi existed near the surface part and most of N. europaea existed at the inner part of the polyethylene glycol (PEG) gel pellet, which had entrapped activated sludge and used in a landfill leachate treatment reactor. It was suggested that this monoclonal antibody method was utilized for estimating and controlling the population of nitrifying bacteria as a quick and favorable tool.

Evaluation of the Efficiency of Protein A Affinity Chromatography to Purify a Monoclonal Antibody for Cancer Treatment and its Purity Analysis

2020 ◽  
Vol 7 (2) ◽  
pp. 121-133
Author(s):  
Ayesha Akhtar ◽  
Shivakumar Arumugam ◽  
Shoaib Alam
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Affinity Chromatography ◽  
Protein A ◽  
Exchange Chromatography ◽  
Size Exclusion ◽  
High Yield ◽  
Staphylococcal Protein A ◽  
Purification Step ◽  
Purity Analysis

Background:: Protein A affinity chromatography is often employed as the most crucial purification step for monoclonal antibodies to achieve high yield with purity and throughput requirements. Introduction:: Protein A, also known as Staphylococcal protein A (SPA) is found in the cell wall of the bacteria staphylococcus aureus. It is one of the first discovered immunoglobulin binding molecules and has been extensively studied since the past few decades. The efficiency of Protein A affinity chromatography to purify a recombinant monoclonal antibody in a cell culture sample has been evaluated, which removes 99.0% of feed stream impurities. Materials and Method:: We have systematically evaluated the purification performance by using a battery of analytical methods SDS-PAGE (non-reduced and reduced sample), Cation Exchange Chromatography (CEX), Size-exclusion chromatography (SEC), and Reversed phased-Reduced Chromatography for a CHO-derived monoclonal antibody. Results and Discussion:: The analytical test was conducted to determine the impurity parameter, Host Cell Contaminating Proteins (HCP). It was evaluated to be 0.015ng/ml after the purification step; while initially, it was found to be 24.431ng/ml. Conclusion:: The tests showed a distinct decrease in the level of different impurities after the chromatography step. It can be concluded that Protein A chromatography is an efficient step in the purification of monoclonal antibodies.

scholarly journals Development of a New Highly Selective Monoclonal Antibody against Preferentially Expressed Antigen in Melanoma (PRAME) and Identification of the Target Epitope by Bio-Layer Interferometry

2021 ◽  
Vol 22 (6) ◽  
pp. 3166
Author(s):  
Jwala Priyadarsini Sivaccumar ◽  
Antonio Leonardi ◽  
Emanuela Iaccarino ◽  
Giusy Corvino ◽  
Luca Sanguigno ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Western Blotting ◽  
Cancer Biomarkers ◽  
Trypsin Digestion ◽  
Protein Fragments ◽  
Target Epitope ◽  
Potential Activity ◽  
Antibody Epitopes

Background: Monoclonal antibodies (mAbs) against cancer biomarkers are key reagents in diagnosis and therapy. One such relevant biomarker is a preferentially expressed antigen in melanoma (PRAME) that is selectively expressed in many tumors. Knowing mAb’s epitope is of utmost importance for understanding the potential activity and therapeutic prospective of the reagents. Methods: We generated a mAb against PRAME immunizing mice with PRAME fragment 161–415; the affinity of the antibody for the protein was evaluated by ELISA and SPR, and its ability to detect the protein in cells was probed by cytofluorimetry and Western blotting experiments. The antibody epitope was identified immobilizing the mAb on bio-layer interferometry (BLI) sensor chip, capturing protein fragments obtained following trypsin digestion and performing mass spectrometry analyses. Results: A mAb against PRAME with an affinity of 35 pM was obtained and characterized. Its epitope on PRAME was localized on residues 202–212, taking advantage of the low volumes and lack of fluidics underlying the BLI settings. Conclusions: The new anti-PRAME mAb recognizes the folded protein on the surface of cell membranes suggesting that the antibody’s epitope is well exposed. BLI sensor chips can be used to identify antibody epitopes.

A novel method for the non-chromatographic purification of technetium-99m-labeled monoclonal antibodies: a study with B72.3 monoclonal antibody

1994 ◽  
Vol 21 (2) ◽  
pp. 171-178 ◽  
Author(s):  
Howard S. Rosenzweig ◽  
Girish N. Ranadive ◽  
Troy Seskey ◽  
Michael W. Epperly ◽  
William D. Bloomer
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Chromatographic Purification ◽  
Technetium 99M ◽  
Novel Method

scholarly journals Possible Future Monoclonal Antibody (mAb)-Based Therapy against Arbovirus Infections

2013 ◽  
Vol 2013 ◽  
pp. 1-21 ◽  
Author(s):  
Giuseppe Sautto ◽  
Nicasio Mancini ◽  
Giacomo Gorini ◽  
Massimo Clementi ◽  
Roberto Burioni
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Side Effects ◽  
Antiviral Activity ◽  
The Other ◽  
Viral Escape ◽  
Passive Immunotherapy ◽  
Medical Need

More than 150 arboviruses belonging to different families are known to infect humans, causing endemic infections as well as epidemic outbreaks. Effective vaccines to limit the occurrence of some of these infections have been licensed, while for the others several new immunogens are under development mostly for their improvements concerning safety and effectiveness profiles. On the other hand, specific and effective antiviral drugs are not yet available, posing an urgent medical need in particular for emergency cases. Neutralizing monoclonal antibodies (mAbs) have been demonstrated to be effective in the treatment of several infectious diseases as well as in preliminaryin vitroandin vivomodels of arbovirus-related infections. Given their specific antiviral activity as well-tolerated molecules with limited side effects, mAbs could represent a new therapeutic approach for the development of an effective treatment, as well as useful tools in the study of the host-virus interplay and in the development of more effective immunogens. However, before their use as candidate therapeutics, possible hurdles (e.g., Ab-dependent enhancement of infection, occurrence of viral escape variants) must be carefully evaluated. In this review are described the main arboviruses infecting humans and candidate mAbs to be possibly used in a future passive immunotherapy.

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