Special Issue "Monoclonal Antibodies"

A special issue of Antibodies (ISSN 2073-4468).

Deadline for manuscript submissions: closed (31 October 2017)

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Guest Editor
Dr. Christian Klein

Roche Pharmaceutical Research & Early Development, Switzerland
Website | E-Mail
Interests: immunotherapy of cancer; bispecific antibodies

Special Issue Information

Dear Colleagues,

Monoclonal antibodies are established in clinical practice for the treatment of cancer, and autoimmune and infectious diseases. The first generation of antibodies has been dominated by classical IgG antibodies, however, in the last decade, the field has advanced, and, nowadays, a large proportion of antibodies in development have been engineered.  This Special Issue on "Monoclonal Antibodies" will cover original manuscripts and reviews in the field of the development of classical monoclonal antibodies that address novel biology, as well as progress in the engineering of novel antibody formats, including antibody drug conjugates, bispecific antibodies, and antibody-like scaffolds.

Dr. Christian Klein
Guest Editor

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 papers will be 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. Antibodies is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 350 CHF (Swiss Francs). 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

  • monoclonal antibodies
  • engineered antibodies
  • bispecific antibodies
  • antibody drug conjugates
  • antibody-like scaffolds

Published Papers (14 papers)

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Editorial

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Open AccessEditorial Special Issue: Monoclonal Antibodies
Antibodies 2018, 7(2), 17; doi:10.3390/antib7020017
Received: 27 March 2018 / Revised: 8 April 2018 / Accepted: 9 April 2018 / Published: 10 April 2018
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Abstract
Monoclonal antibodies are utilized in clinical practice for the treatment of various diseases including cancer, autoimmunity, metabolic and infectious diseases [...]
Full article
(This article belongs to the Special Issue Monoclonal Antibodies) Printed Edition available

Research

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Open AccessArticle Tumor-Directed Blockade of CD47 with Bispecific Antibodies Induces Adaptive Antitumor Immunity
Antibodies 2018, 7(1), 3; doi:10.3390/antib7010003
Received: 30 October 2017 / Revised: 22 December 2017 / Accepted: 22 December 2017 / Published: 3 January 2018
Cited by 1 | PDF Full-text (2032 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
CD47 serves as an anti-phagocytic receptor that is upregulated by cancer to promote immune escape. As such, CD47 is the focus of intense immuno-oncology drug development efforts. However, as CD47 is expressed ubiquitously, clinical development of conventional drugs, e.g., monoclonal antibodies, is confronted
[...] Read more.
CD47 serves as an anti-phagocytic receptor that is upregulated by cancer to promote immune escape. As such, CD47 is the focus of intense immuno-oncology drug development efforts. However, as CD47 is expressed ubiquitously, clinical development of conventional drugs, e.g., monoclonal antibodies, is confronted with patient safety issues and poor pharmacology due to the widespread CD47 “antigen sink”. A potential solution is tumor-directed blockade of CD47, which can be achieved with bispecific antibodies (biAbs). Using mouse CD47-blocking biAbs in a syngeneic tumor model allowed us to evaluate the efficacy of tumor-directed blockade of CD47 in the presence of the CD47 antigen sink and a functional adaptive immune system. We show here that CD47-targeting biAbs inhibited tumor growth in vivo, promoting durable antitumor responses and stimulating CD8+ T cell activation in vitro. In vivo efficacy of the biAbs could be further enhanced when combined with chemotherapy or PD-1/PD-L1 immune checkpoint blockade. We also show that selectivity and pharmacological properties of the biAb are dependent on the affinity of the anti-CD47 arm. Taken together, our study validates the approach to use CD47-blocking biAbs either as a monotherapy or part of a multi-drug approach to enhance antitumor immunity. Full article
(This article belongs to the Special Issue Monoclonal Antibodies) Printed Edition available
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Open AccessFeature PaperArticle Controlling the Glycosylation Profile in mAbs Using Time-Dependent Media Supplementation
Antibodies 2018, 7(1), 1; doi:10.3390/antib7010001
Received: 16 October 2017 / Revised: 23 November 2017 / Accepted: 15 December 2017 / Published: 21 December 2017
Cited by 1 | PDF Full-text (4116 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In order to meet desired drug product quality targets, the glycosylation profile of biotherapeutics such as monoclonal antibodies (mAbs) must be maintained consistently during manufacturing. Achieving consistent glycan distribution profiles requires identifying factors that influence glycosylation, and manipulating them appropriately via well-designed control
[...] Read more.
In order to meet desired drug product quality targets, the glycosylation profile of biotherapeutics such as monoclonal antibodies (mAbs) must be maintained consistently during manufacturing. Achieving consistent glycan distribution profiles requires identifying factors that influence glycosylation, and manipulating them appropriately via well-designed control strategies. Now, the cell culture media supplement, MnCl2, is known to alter the glycosylation profile in mAbs generally, but its effect, particularly when introduced at different stages during cell growth, has yet to be investigated and quantified. In this study, we evaluate the effect of time-dependent addition of MnCl2 on the glycan profile quantitatively, using factorial design experiments. Our results show that MnCl2 addition during the lag and exponential phases affects the glycan profile significantly more than stationary phase supplementation does. Also, using a novel computational technique, we identify various combinations of glycan species that are affected by this dynamic media supplementation scheme, and quantify the effects mathematically. Our experiments demonstrate the importance of taking into consideration the time of addition of these trace supplements, not just their concentrations, and our computational analysis provides insight into what supplements to add, when, and how much, in order to induce desired changes. Full article
(This article belongs to the Special Issue Monoclonal Antibodies) Printed Edition available
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Open AccessArticle Characterization of Monoclonal Antibody–Protein Antigen Complexes Using Small-Angle Scattering and Molecular Modeling
Antibodies 2017, 6(4), 25; doi:10.3390/antib6040025
Received: 16 November 2017 / Revised: 7 December 2017 / Accepted: 8 December 2017 / Published: 15 December 2017
Cited by 1 | PDF Full-text (35215 KB) | HTML Full-text | XML Full-text
Abstract
The determination of monoclonal antibody interactions with protein antigens in solution can lead to important insights guiding physical characterization and molecular engineering of therapeutic targets. We used small-angle scattering (SAS) combined with size-exclusion multi-angle light scattering high-performance liquid chromatography to obtain monodisperse samples
[...] Read more.
The determination of monoclonal antibody interactions with protein antigens in solution can lead to important insights guiding physical characterization and molecular engineering of therapeutic targets. We used small-angle scattering (SAS) combined with size-exclusion multi-angle light scattering high-performance liquid chromatography to obtain monodisperse samples with defined stoichiometry to study an anti-streptavidin monoclonal antibody interacting with tetrameric streptavidin. Ensembles of structures with both monodentate and bidentate antibody–antigen complexes were generated using molecular docking protocols and molecular simulations. By comparing theoretical SAS profiles to the experimental data it was determined that the primary component(s) were compact monodentate and/or bidentate complexes. SAS profiles of extended monodentate complexes were not consistent with the experimental data. These results highlight the capability for determining the shape of monoclonal antibody–antigen complexes in solution using SAS data and physics-based molecular modeling. Full article
(This article belongs to the Special Issue Monoclonal Antibodies) Printed Edition available
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Open AccessArticle Process Analytical Approach towards Quality Controlled Process Automation for the Downstream of Protein Mixtures by Inline Concentration Measurements Based on Ultraviolet/Visible Light (UV/VIS) Spectral Analysis
Antibodies 2017, 6(4), 24; doi:10.3390/antib6040024
Received: 31 October 2017 / Revised: 29 November 2017 / Accepted: 6 December 2017 / Published: 12 December 2017
Cited by 2 | PDF Full-text (3618 KB) | HTML Full-text | XML Full-text
Abstract
Downstream of pharmaceutical proteins, such as monoclonal antibodies, is mainly done by chromatography, where concentration determination of coeluting components presents a major problem. Inline concentration measurements (ICM) by Ultraviolet/Visible light (UV/VIS)-spectral data analysis provide a label-free and noninvasive approach to significantly speed up
[...] Read more.
Downstream of pharmaceutical proteins, such as monoclonal antibodies, is mainly done by chromatography, where concentration determination of coeluting components presents a major problem. Inline concentration measurements (ICM) by Ultraviolet/Visible light (UV/VIS)-spectral data analysis provide a label-free and noninvasive approach to significantly speed up the analysis and process time. Here, two different approaches are presented. For a test mixture of three proteins, a fast and easily calibrated method based on the non-negative least-squares algorithm is shown, which reduces the calibration effort compared to a partial least-squares approach. The accuracy of ICM for analytical separations of three proteins on an ion exchange column is over 99%, compared to less than 85% for classical peak area evaluation. The power of the partial least squares algorithm (PLS) is shown by measuring the concentrations of Immunoglobulin G (IgG) monomer and dimer under a worst-case scenario of completely overlapping peaks. Here, the faster SIMPLS algorithm is used in comparison to the nonlinear iterative partial least squares (NIPALS) algorithm. Both approaches provide concentrations as well as purities in real-time, enabling live-pooling decisions based on product quality. This is one important step towards advanced process automation of chromatographic processes. Analysis time is less than 100 ms and only one program is used for all the necessary communications and calculations. Full article
(This article belongs to the Special Issue Monoclonal Antibodies) Printed Edition available
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Open AccessArticle Generation and Performance of R132H Mutant IDH1 Rabbit Monoclonal Antibody
Antibodies 2017, 6(4), 22; doi:10.3390/antib6040022
Received: 31 October 2017 / Revised: 21 November 2017 / Accepted: 22 November 2017 / Published: 1 December 2017
Cited by 1 | PDF Full-text (3849 KB) | HTML Full-text | XML Full-text
Abstract
Isocitrate dehydrogenase 1 (IDH1) gene mutations have been observed in a majority of diffuse astrocytomas, oligodendrogliomas, and secondary glioblastomas, and the mutant IDH1 R132H is detectable in most of these lesions. By specifically targeting the R132H mutation through B-cell cloning, a novel rabbit
[...] Read more.
Isocitrate dehydrogenase 1 (IDH1) gene mutations have been observed in a majority of diffuse astrocytomas, oligodendrogliomas, and secondary glioblastomas, and the mutant IDH1 R132H is detectable in most of these lesions. By specifically targeting the R132H mutation through B-cell cloning, a novel rabbit monoclonal antibody, MRQ-67, was produced that can recognize mutant IDH1 R132H and does not react with the wild type protein as demonstrated by Enzyme-linked immunosorbent assay (ELISA) and Western blotting. Through immunohistochemistry, the antibody is able to highlight neoplastic cells in glioma tissue specimens, and can be used as a tool in glioma subtyping. Immunohistochemistry (IHC) detection of IDH1 mutant protein may also be used to visualize single infiltrating tumor cells in surrounding brain tissue with an otherwise normal appearance. Full article
(This article belongs to the Special Issue Monoclonal Antibodies) Printed Edition available
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Open AccessArticle Integration of Aqueous Two-Phase Extraction as Cell Harvest and Capture Operation in the Manufacturing Process of Monoclonal Antibodies
Antibodies 2017, 6(4), 21; doi:10.3390/antib6040021
Received: 30 October 2017 / Revised: 17 November 2017 / Accepted: 20 November 2017 / Published: 1 December 2017
Cited by 1 | PDF Full-text (7789 KB) | HTML Full-text | XML Full-text
Abstract
Substantial improvements have been made to cell culturing processes (e.g., higher product titer) in recent years by raising cell densities and optimizing cultivation time. However, this has been accompanied by an increase in product-related impurities and therefore greater challenges in subsequent clarification and
[...] Read more.
Substantial improvements have been made to cell culturing processes (e.g., higher product titer) in recent years by raising cell densities and optimizing cultivation time. However, this has been accompanied by an increase in product-related impurities and therefore greater challenges in subsequent clarification and capture operations. Considering the paradigm shift towards the design of continuously operating dedicated plants at smaller scales—with or without disposable technology—for treating smaller patient populations due to new indications or personalized medicine approaches, the rising need for new, innovative strategies for both clarification and capture technology becomes evident. Aqueous two-phase extraction (ATPE) is now considered to be a feasible unit operation, e.g., for the capture of monoclonal antibodies or recombinant proteins. However, most of the published work so far investigates the applicability of ATPE in antibody-manufacturing processes at the lab-scale and for the most part, only during the capture step. This work shows the integration of ATPE as a combined harvest and capture step into a downstream process. Additionally, a model is applied that allows early prediction of settler dimensions with high prediction accuracy. Finally, a reliable process development concept, which guides through the necessary steps, starting from the definition of the separation task to the final stages of integration and scale-up, is presented. Full article
(This article belongs to the Special Issue Monoclonal Antibodies) Printed Edition available
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Open AccessArticle Epitope Sequences in Dengue Virus NS1 Protein Identified by Monoclonal Antibodies
Antibodies 2017, 6(4), 14; doi:10.3390/antib6040014
Received: 8 August 2017 / Revised: 22 September 2017 / Accepted: 22 September 2017 / Published: 15 October 2017
Cited by 1 | PDF Full-text (3012 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Dengue nonstructural protein 1 (NS1) is a multi-functional glycoprotein with essential functions both in viral replication and modulation of host innate immune responses. NS1 has been established as a good surrogate marker for infection. In the present study, we generated four anti-NS1 monoclonal
[...] Read more.
Dengue nonstructural protein 1 (NS1) is a multi-functional glycoprotein with essential functions both in viral replication and modulation of host innate immune responses. NS1 has been established as a good surrogate marker for infection. In the present study, we generated four anti-NS1 monoclonal antibodies against recombinant NS1 protein from dengue virus serotype 2 (DENV2), which were used to map three NS1 epitopes. The sequence 193AVHADMGYWIESALNDT209 was recognized by monoclonal antibodies 2H5 and 4H1BC, which also cross-reacted with Zika virus (ZIKV) protein. On the other hand, the sequence 25VHTWTEQYKFQPES38 was recognized by mAb 4F6 that did not cross react with ZIKV. Lastly, a previously unidentified DENV2 NS1-specific epitope, represented by the sequence 127ELHNQTFLIDGPETAEC143, is described in the present study after reaction with mAb 4H2, which also did not cross react with ZIKV. The selection and characterization of the epitope, specificity of anti-NS1 mAbs, may contribute to the development of diagnostic tools able to differentiate DENV and ZIKV infections. Full article
(This article belongs to the Special Issue Monoclonal Antibodies) Printed Edition available
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Open AccessArticle Host Cell Proteins in Biologics Manufacturing: The Good, the Bad, and the Ugly
Antibodies 2017, 6(3), 13; doi:10.3390/antib6030013
Received: 17 August 2017 / Revised: 8 September 2017 / Accepted: 10 September 2017 / Published: 16 September 2017
Cited by 3 | PDF Full-text (3471 KB) | HTML Full-text | XML Full-text
Abstract
Significant progress in the manufacturing of biopharmaceuticals has been made by increasing the overall titers in the USP (upstream processing) titers without raising the cost of the USP. In addition, the development of platform processes led to a higher process robustness. Despite or
[...] Read more.
Significant progress in the manufacturing of biopharmaceuticals has been made by increasing the overall titers in the USP (upstream processing) titers without raising the cost of the USP. In addition, the development of platform processes led to a higher process robustness. Despite or even due to those achievements, novel challenges are in sight. The higher upstream titers created more complex impurity profiles, both in mass and composition, demanding higher separation capacities and selectivity in downstream processing (DSP). This creates a major shift of costs from USP to DSP. In order to solve this issue, USP and DSP integration approaches can be developed and used for overall process optimization. This study focuses on the characterization and classification of host cell proteins (HCPs) in each unit operation of the DSP (i.e., aqueous two-phase extraction, integrated countercurrent chromatography). The results create a data-driven feedback to the USP, which will serve for media and process optimizations in order to reduce, or even eliminate nascent critical HCPs. This will improve separation efficiency and may lead to a quantitative process understanding. Different HCP species were classified by stringent criteria with regard to DSP separation parameters into “The Good, the Bad, and the Ugly” in terms of pI and MW using 2D-PAGE analysis depending on their positions on the gels. Those spots were identified using LC-MS/MS analysis. HCPs, which are especially difficult to remove and persistent throughout the DSP (i.e., “Bad” or “Ugly”), have to be evaluated by their ability to be separated. In this approach, HCPs, considered “Ugly,” represent proteins with a MW larger than 15 kDa and a pI between 7.30 and 9.30. “Bad” HCPs can likewise be classified using MW (>15 kDa) and pI (4.75–7.30 and 9.30–10.00). HCPs with a MW smaller than 15 kDa and a pI lower than 4.75 and higher than 10.00 are classified as “Good” since their physicochemical properties differ significantly from the product. In order to evaluate this classification scheme, it is of utmost importance to use orthogonal analytical methods such as IEX, HIC, and SEC. Full article
(This article belongs to the Special Issue Monoclonal Antibodies) Printed Edition available
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Open AccessArticle Functional, Biophysical, and Structural Characterization of Human IgG1 and IgG4 Fc Variants with Ablated Immune Functionality
Antibodies 2017, 6(3), 12; doi:10.3390/antib6030012
Received: 19 July 2017 / Revised: 20 August 2017 / Accepted: 21 August 2017 / Published: 1 September 2017
Cited by 1 | PDF Full-text (5951 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Engineering of fragment crystallizable (Fc) domains of therapeutic immunoglobulin (IgG) antibodies to eliminate their immune effector functions while retaining other Fc characteristics has numerous applications, including blocking antigens on Fc gamma (Fcγ) receptor-expressing immune cells. We previously reported on a human IgG2 variant
[...] Read more.
Engineering of fragment crystallizable (Fc) domains of therapeutic immunoglobulin (IgG) antibodies to eliminate their immune effector functions while retaining other Fc characteristics has numerous applications, including blocking antigens on Fc gamma (Fcγ) receptor-expressing immune cells. We previously reported on a human IgG2 variant termed IgG2σ with barely detectable activity in antibody-dependent cellular cytotoxicity, phagocytosis, complement activity, and Fcγ receptor binding assays. Here, we extend that work to IgG1 and IgG4 antibodies, alternative subtypes which may offer advantages over IgG2 antibodies. In several in vitro and in vivo assays, the IgG1σ and IgG4σ variants showed equal or even lower Fc-related activities than the corresponding IgG2σ variant. In particular, IgG1σ and IgG4σ variants demonstrate complete lack of effector function as measured by antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, antibody-dependent cellular phagocytosis, and in vivo T-cell activation. The IgG1σ and IgG4σ variants showed acceptable solubility and stability, and typical human IgG1 pharmacokinetic profiles in human FcRn-transgenic mice and cynomolgus monkeys. In silico T-cell epitope analyses predict a lack of immunogenicity in humans. Finally, crystal structures and simulations of the IgG1σ and IgG4σ Fc domains can explain the lack of Fc-mediated immune functions. These variants show promise for use in those therapeutic antibodies and Fc fusions for which the Fc domain should be immunologically “silent”. Full article
(This article belongs to the Special Issue Monoclonal Antibodies) Printed Edition available
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Open AccessArticle Monoclonal Antibodies against Plasmodium falciparum Circumsporozoite Protein
Antibodies 2017, 6(3), 11; doi:10.3390/antib6030011
Received: 10 May 2017 / Revised: 14 June 2017 / Accepted: 1 August 2017 / Published: 23 August 2017
Cited by 1 | PDF Full-text (2242 KB) | HTML Full-text | XML Full-text
Abstract
Malaria is a mosquito-borne infectious disease caused by the parasite Plasmodium spp. Malaria continues to have a devastating impact on human health. Sporozoites are the infective forms of the parasite inside mosquito salivary glands. Circumsporozoite protein (CSP) is a major and immunodominant protective
[...] Read more.
Malaria is a mosquito-borne infectious disease caused by the parasite Plasmodium spp. Malaria continues to have a devastating impact on human health. Sporozoites are the infective forms of the parasite inside mosquito salivary glands. Circumsporozoite protein (CSP) is a major and immunodominant protective antigen on the surface of Plasmodium sporozoites. Here, we report a generation of specific monoclonal antibodies that recognize the central repeat and C-terminal regions of P. falciparum CSP. The monoclonal antibodies 3C1, 3C2, and 3D3—specific for the central repeat region—have higher titers and protective efficacies against challenge with sporozoites compared with 2A10, a gold standard monoclonal antibody that was generated in early 1980s. Full article
(This article belongs to the Special Issue Monoclonal Antibodies) Printed Edition available
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Review

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Open AccessReview Infusion Reactions Associated with the Medical Application of Monoclonal Antibodies: The Role of Complement Activation and Possibility of Inhibition by Factor H
Antibodies 2018, 7(1), 14; doi:10.3390/antib7010014
Received: 24 December 2017 / Revised: 1 March 2018 / Accepted: 8 March 2018 / Published: 14 March 2018
Cited by 1 | PDF Full-text (533 KB) | HTML Full-text | XML Full-text
Abstract
Human application of monoclonal antibodies (mAbs), enzymes, as well as contrast media and many other particulate drugs and agents referred to as “nanomedicines”, can initiate pseudoallergic hypersensitivity reactions, also known as infusion reactions. These may in part be mediated by the activation of
[...] Read more.
Human application of monoclonal antibodies (mAbs), enzymes, as well as contrast media and many other particulate drugs and agents referred to as “nanomedicines”, can initiate pseudoallergic hypersensitivity reactions, also known as infusion reactions. These may in part be mediated by the activation of the complement system, a major humoral defense system of innate immunity. In this review, we provide a brief outline of complement activation-related pseudoallergy (CARPA) in general, and then focus on the reactions caused by mAb therapy. Because the alternative pathway of complement activation may amplify such adverse reactions, we highlight the potential use of complement factor H as an inhibitor of CARPA. Full article
(This article belongs to the Special Issue Monoclonal Antibodies) Printed Edition available
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Open AccessReview Pharmacokinetic and Pharmacodynamic Considerations for the Use of Monoclonal Antibodies in the Treatment of Bacterial Infections
Antibodies 2018, 7(1), 5; doi:10.3390/antib7010005
Received: 8 December 2017 / Revised: 1 January 2018 / Accepted: 2 January 2018 / Published: 4 January 2018
Cited by 2 | PDF Full-text (255 KB) | HTML Full-text | XML Full-text
Abstract
Antibiotic-resistant bacterial pathogens are increasingly implicated in hospital- and community-acquired infections. Recent advances in monoclonal antibody (mAb) production and engineering have led to renewed interest in the development of antibody-based therapies for treatment of drug-resistant bacterial infections. Currently, there are three antibacterial mAb
[...] Read more.
Antibiotic-resistant bacterial pathogens are increasingly implicated in hospital- and community-acquired infections. Recent advances in monoclonal antibody (mAb) production and engineering have led to renewed interest in the development of antibody-based therapies for treatment of drug-resistant bacterial infections. Currently, there are three antibacterial mAb products approved by the Food and Drug Administration (FDA) and at least nine mAbs are in clinical trials. Antibacterial mAbs are typically developed to kill bacteria or to attenuate bacterial pathological activity through neutralization of bacterial toxins and virulence factors. Antibodies exhibit distinct pharmacological mechanisms from traditional antimicrobials and, hence, cross-resistance between small molecule antimicrobials and antibacterial mAbs is unlikely. Additionally, the long biological half-lives typically found for mAbs may allow convenient dosing and vaccine-like prophylaxis from infection. However, the high affinity of mAbs and the involvement of the host immune system in their pharmacological actions may lead to complex and nonlinear pharmacokinetics and pharmacodynamics. In this review, we summarize the pharmacokinetics and pharmacodynamics of the FDA-approved antibacterial mAbs and those are currently in clinical trials. Challenges in the development of antibacterial mAbs are also discussed. Full article
(This article belongs to the Special Issue Monoclonal Antibodies) Printed Edition available
Open AccessReview Monoclonal Antibody: A New Treatment Strategy against Multiple Myeloma
Antibodies 2017, 6(4), 18; doi:10.3390/antib6040018
Received: 20 October 2017 / Revised: 9 November 2017 / Accepted: 10 November 2017 / Published: 14 November 2017
Cited by 1 | PDF Full-text (1485 KB) | HTML Full-text | XML Full-text
Abstract
2015 was a groundbreaking year for the multiple myeloma community partly due to the breakthrough approval of the first two monoclonal antibodies in the treatment for patients with relapsed and refractory disease. Despite early disappointments, monoclonal antibodies targeting CD38 (daratumumab) and signaling lymphocytic
[...] Read more.
2015 was a groundbreaking year for the multiple myeloma community partly due to the breakthrough approval of the first two monoclonal antibodies in the treatment for patients with relapsed and refractory disease. Despite early disappointments, monoclonal antibodies targeting CD38 (daratumumab) and signaling lymphocytic activation molecule F7 (SLAMF7) (elotuzumab) have become available for patients with multiple myeloma in the same year. Specifically, phase 3 clinical trials of combination therapies incorporating daratumumab or elotuzumab indicate both efficacy and a very favorable toxicity profile. These therapeutic monoclonal antibodies for multiple myeloma can kill target cells via antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent phagocytosis, as well as by direct blockade of signaling cascades. In addition, their immunomodulatory effects may simultaneously inhibit the immunosuppressive bone marrow microenvironment and restore the key function of immune effector cells. In this review, we focus on monoclonal antibodies that have shown clinical efficacy or promising preclinical anti-multiple myeloma activities that warrant further clinical development. We summarize mechanisms that account for the in vitro and in vivo anti-myeloma effects of these monoclonal antibodies, as well as relevant preclinical and clinical results. Monoclonal antibody-based immunotherapies have already and will continue to transform the treatment landscape in multiple myeloma. Full article
(This article belongs to the Special Issue Monoclonal Antibodies) Printed Edition available
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