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Monoclonal Antibodies and Their Functional Fragments in Research, Diagnosis and Therapy 2.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Macromolecules".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 21949

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Special Issue Editors

Dr. Menotti Ruvo

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Guest Editor

Istituto di Biostrutture e Bioimmagini, CNR, 80134 Napoli, Italy
Interests: monoclonal antibodies; antibody functional fragments; antibody drug conjugates
Special Issues, Collections and Topics in MDPI journals

Dr. Annamaria Sandomenico

E-Mail Website
Guest Editor

Istituto di Biostrutture e Bioimmagini, CNR, 80134 Napoli, Italy
Interests: proteins; protein expression; molecular biology; cell culture
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Monoclonal antibodies (mAbs) are among the most specialized molecules for the recognition and capture of specific analytes. Hundreds of thousands of mAbs have been generated targeting a large number of different antigens with ever-increasing affinity and specificity and are available for the most diverse purposes. Many of them have been validated as irreplaceable agents for diagnosis and therapy or as unique reagents for research. Others are being developed using a plethora of emerging technologies that provide new molecular tools to overcome the need for animal immunization. This renewed Special Issue will continue to strive to collect prospective visions and to survey new strategic assets adopted by the main research groups engaged in this field, focusing in particular on the generation of new monoclonal or surrogate antibodies, such as Fab, Fab2, ScFv and nanobodies, which have an increasing impact in biomedicine as therapeutic or diagnostic assets in various diseases.

Dr. Menotti Ruvo
Dr. Annamaria Sandomenico
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

mAbs
Fabs
ScFv
Nanobodies
Biomarker detection
Bispecific antibodies
Analyte detection
Sandwich assays

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Published Papers (6 papers)

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Research

18 pages, 2705 KiB

Open AccessArticle

Semi-Automated Cell Panning for Efficient Isolation of FGFR3-Targeting Antibody

by Byeongkwi Min, Minyoung Yoo, Hyeree Kim, Minjung Cho, Do-Hyun Nam and Yeup Yoon

Int. J. Mol. Sci. 2021, 22(12), 6240; https://doi.org/10.3390/ijms22126240 - 9 Jun 2021

Cited by 2 | Viewed by 4543

Abstract

Phage display technology is a widely used practical tool for isolating binding molecules against the desired targets in phage libraries. In the case of targeting the membrane protein with its natural conformation, conventional bio-panning has limitations on the efficient screening of the functionally relevant antibodies. To enrich the single-chain variable fragment (scFv) pools for recognizing the natural conformation of the membrane targets, the conventional bio-panning and screening process was modified to include the semi-automated cell panning protocol. Using FGFR3-overexpressing patient-derived cancer cells, biotin-X-DHPE was introduced and coupled to Streptavidin-coated magnetic beads for use in the solution-phage bio-panning procedure. The resulting clones of scFv were compared to the diversity of the binding region, especially on CDR-H3. The clones enriched further by cell-based panning procedure possessed a similar binding site and the CDR-H3 loop structure. The resulting antibodies inhibited cell growth and induced target degradation. This process may be a useful tool for screening biologically related antibodies that recognize natural conformational structure on cell membrane protein. Furthermore, cell-based panning has the potential to further expand to a high-throughput screening (HTS) system and automation process. Full article

(This article belongs to the Special Issue Monoclonal Antibodies and Their Functional Fragments in Research, Diagnosis and Therapy 2.0)

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17 pages, 4048 KiB

Open AccessArticle

Candida Cell-Surface-Specific Monoclonal Antibodies Protect Mice against Candida auris Invasive Infection

by Jonothan Rosario-Colon, Karen Eberle, Abby Adams, Evan Courville and Hong Xin

Int. J. Mol. Sci. 2021, 22(11), 6162; https://doi.org/10.3390/ijms22116162 - 7 Jun 2021

Cited by 12 | Viewed by 3401

Abstract

Candida auris is a multidrug-resistant fungal pathogen that can cause disseminated bloodstream infections with up to 60% mortality in susceptible populations. Of the three major classes of antifungal drugs, most C. auris isolates show high resistance to azoles and polyenes, with some clinical isolates showing resistance to all three drug classes. We reported in this study a novel approach to treating C. auris disseminated infections through passive transfer of monoclonal antibodies (mAbs) targeting cell surface antigens with high homology in medically important Candida species. Using an established A/J mouse model of disseminated infection that mimics human candidiasis, we showed that C3.1, a mAb that targets β-1,2-mannotriose (β-Man₃), significantly extended survival and reduced fungal burdens in target organs, compared to control mice. We also demonstrated that two peptide-specific mAbs, 6H1 and 9F2, which target hyphal wall protein 1 (Hwp1) and phosphoglycerate kinase 1 (Pgk1), respectively, also provided significantly enhanced survival and reduction of fungal burdens. Finally, we showed that passive transfer of a 6H1+9F2 cocktail induced significantly enhanced protection, compared to treatment with either mAb individually. Our data demonstrate the utility of β-Man₃- and peptide-specific mAbs as an effective alternative to antifungals against medically important Candida species including multidrug-resistant C. auris. Full article

(This article belongs to the Special Issue Monoclonal Antibodies and Their Functional Fragments in Research, Diagnosis and Therapy 2.0)

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20 pages, 3411 KiB

Open AccessArticle

A Nano-Emulsion Platform Functionalized with a Fully Human scFv-Fc Antibody for Atheroma Targeting: Towards a Theranostic Approach to Atherosclerosis

by Samuel Bonnet, Geoffrey Prévot, Stéphane Mornet, Marie-Josée Jacobin-Valat, Yannick Mousli, Audrey Hemadou, Mathieu Duttine, Aurélien Trotier, Stéphane Sanchez, Martine Duonor-Cérutti, Sylvie Crauste-Manciet and Gisèle Clofent-Sanchez

Int. J. Mol. Sci. 2021, 22(10), 5188; https://doi.org/10.3390/ijms22105188 - 14 May 2021

Cited by 17 | Viewed by 2998

Abstract

Atherosclerosis is at the onset of the cardiovascular diseases that are among the leading causes of death worldwide. Currently, high-risk plaques, also called vulnerable atheromatous plaques, remain often undiagnosed until the occurrence of severe complications, such as stroke or myocardial infarction. Molecular imaging agents that target high-risk atheromatous lesions could greatly improve the diagnosis of atherosclerosis by identifying sites of high disease activity. Moreover, a “theranostic approach” that combines molecular imaging agents (for diagnosis) and therapeutic molecules would be of great value for the local management of atheromatous plaques. The aim of this study was to develop and characterize an innovative theranostic tool for atherosclerosis. We engineered oil-in-water nano-emulsions (NEs) loaded with superparamagnetic iron oxide (SPIO) nanoparticles for magnetic resonance imaging (MRI) purposes. Dynamic MRI showed that NE-SPIO nanoparticles decorated with a polyethylene glycol (PEG) layer reduced their liver uptake and extended their half-life. Next, the NE-SPIO-PEG formulation was functionalized with a fully human scFv-Fc antibody (P3) recognizing galectin 3, an atherosclerosis biomarker. The P3-functionalized formulation targeted atheromatous plaques, as demonstrated in an immunohistochemistry analyses of mouse aorta and human artery sections and in an Apoe^−/− mouse model of atherosclerosis. Moreover, the formulation was loaded with SPIO nanoparticles and/or alpha-tocopherol to be used as a theranostic tool for atherosclerosis imaging (SPIO) and for delivery of drugs that reduce oxidation (here, alpha-tocopherol) in atheromatous plaques. This study paves the way to non-invasive targeted imaging of atherosclerosis and synergistic therapeutic applications. Full article

(This article belongs to the Special Issue Monoclonal Antibodies and Their Functional Fragments in Research, Diagnosis and Therapy 2.0)

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12 pages, 1517 KiB

Open AccessArticle

Phage Display Screening of Bovine Antibodies to Foot-and-Mouth Disease Virus and Their Application in a Competitive ELISA for Serodiagnosis

by Sukyo Jeong, Hyun Joo Ahn, Kyung Jin Min, Jae Won Byun, Hyun Mi Pyo, Mi Young Park, Bok Kyung Ku, Jinju Nah, Soyoon Ryoo, Sung Hwan Wee and Sang Jick Kim

Int. J. Mol. Sci. 2021, 22(9), 4328; https://doi.org/10.3390/ijms22094328 - 21 Apr 2021

Cited by 5 | Viewed by 2316

Abstract

For serodiagnosis of foot-and-mouth disease virus (FMDV), monoclonal antibody (MAb)-based competitive ELISA (cELISA) is commonly used since it allows simple and reproducible detection of antibody response to FMDV. However, the use of mouse-origin MAb as a detection reagent is questionable, as antibody responses to FMDV in mice may differ in epitope structure and preference from those in natural hosts such as cattle and pigs. To take advantage of natural host-derived antibodies, a phage-displayed scFv library was constructed from FMDV-immune cattle and subjected to two separate pannings against inactivated FMDV type O and A. Subsequent ELISA screening revealed high-affinity scFv antibodies specific to a serotype (O or A) as well as those with pan-serotype specificity. When BvO17, an scFv antibody specific to FMDV type O, was tested as a detection reagent in cELISA, it successfully detected FMDV type O antibodies for both serum samples from vaccinated cattle and virus-challenged pigs with even higher sensitivity than a mouse MAb-based commercial FMDV type O antibody detection kit. These results demonstrate the feasibility of using natural host-derived antibodies such as bovine scFv instead of mouse MAb in cELISA for serological detection of antibody response to FMDV in the susceptible animals. Full article

(This article belongs to the Special Issue Monoclonal Antibodies and Their Functional Fragments in Research, Diagnosis and Therapy 2.0)

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15 pages, 5534 KiB

Open AccessArticle

Monoclonal Antibody Aggregation Associated with Free Radical Induced Oxidation

by Kai Zheng, Diya Ren, Y. John Wang, Wayne Lilyestrom, Thomas Scherer, Justin K. Y. Hong and Junyan A. Ji

Int. J. Mol. Sci. 2021, 22(8), 3952; https://doi.org/10.3390/ijms22083952 - 12 Apr 2021

Cited by 13 | Viewed by 4082

Abstract

Oxidation is an important degradation pathway of protein drugs. The susceptibility to oxidation is a common concern for therapeutic proteins as it may impact product efficacy and patient safety. In this work, we used 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH) as an oxidative stress reagent to evaluate the oxidation of therapeutic antibodies. In addition to the oxidation of methionine (Met) and tryptophan (Trp) residues, we also observed an increase of protein aggregation. Size-exclusion chromatography and multi-angle light scattering showed that the soluble aggregates induced by AAPH consist of dimer, tetramer, and higher-order aggregate species. Sodium dodecyl sulfate polyacrylamide gel electrophoresis indicated that inter-molecular disulfide bonds contributed to the protein aggregation. Furthermore, intrinsic fluorescence spectra suggested that dimerization of tyrosine (Tyr) residues could account for the non-reducible cross-links. An excipient screening study demonstrated that Trp, pyridoxine, or Tyr could effectively reduce protein aggregation due to oxidative stress. This work provides valuable insight into the mechanisms of oxidative-stress induced protein aggregation, as well as strategies to minimize such aggregate formation during the development and storage of therapeutic proteins. Full article

(This article belongs to the Special Issue Monoclonal Antibodies and Their Functional Fragments in Research, Diagnosis and Therapy 2.0)

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16 pages, 2641 KiB

Open AccessArticle

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

by Jwala Priyadarsini Sivaccumar, Antonio Leonardi, Emanuela Iaccarino, Giusy Corvino, Luca Sanguigno, Angela Chambery, Rosita Russo, Mariangela Valletta, Debora Latino, Domenica Capasso, Nunzianna Doti, Menotti Ruvo and Annamaria Sandomenico

Int. J. Mol. Sci. 2021, 22(6), 3166; https://doi.org/10.3390/ijms22063166 - 20 Mar 2021

Cited by 7 | Viewed by 3358

Abstract

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. Full article

(This article belongs to the Special Issue Monoclonal Antibodies and Their Functional Fragments in Research, Diagnosis and Therapy 2.0)

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