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Special Issue "Recent Advances in Therapeutic Antibody"

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A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Biopharmaceutics".

Deadline for manuscript submissions: 30 September 2023 | Viewed by 5005

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Special Issue Editor

Dr. Isabelle Turbica

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Guest Editor

Inserm, Inflammation, Microbiome and Immunosurveillance, Université Paris-Saclay, 92290 Châtenay-Malabry, France
Interests: immunogenicity; therapeutic antibody; aggregates; innate immune reponse; T-cell repertoire

Special Issue Information

Dear Colleagues,

The development of therapeutic monoclonal antibodies (mAbs) has remarkably evolved over the past 10 years, and healthcare will still be largely driven by these biologics for the foreseeable decades. Indeed, the number of full-length mAbs, including biosimilars, and derivatives such as Fc-fusion proteins or drug-conjugates, are now part of the therapeutic arsenal. In particular, the arrival of antibodies modulating the immune checkpoints has brought a significant improvement in the field of oncology, while successes in the field of inflammation and autoimmunity have also been confirmed. However, other medical areas covered by the use of mAbs have also expanded, resulting in many new indications. With regard to new formats, multi-specific and novel shapes, such as nanobodies, are mostly in earlier stages of development, but the way forward is promising and exciting.

All these new and rapid advances require frequent updates, and we are pleased to invite you to be part of this Special Issue, in order to share your contributions to the development of therapeutic mAbs.

The aim is to gain insight the following topics: development of novel forms of antibody products, optimization of next-generation products, towards the engineering methods to improve the pharmacokinetics or efficacy/specificity, reduce immunogenicity, etc. New topics about (but not limited to) the improvement of the production processes, including producing-cells engineering, analytical methods improvement, and new formulations, are also welcome.

This Special Issue will be composed of original research articles and reviews. We are looking forward to receiving your contributions. Let us see what is really recent in the therapeutic antibodies area.

Dr. Isabelle Turbica
Guest Editor

Manuscript Submission Information

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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. Pharmaceutics is an international peer-reviewed open access monthly 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 2600 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

antibody engineering
antibody optimization
next-generation antibodies (biobetter)
biosimilars
antibody manufacturing
protein formulation
immunogenicity reduction
analytical antibody characterization
antibody drug conjugates (ADCs)
bispecific and multispecific antibodies
nanobodies
antibody fragments

Published Papers (5 papers)

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Research

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Open AccessArticle

The Screening of Broadly Neutralizing Antibodies Targeting the SARS-CoV-2 Spike Protein by mRNA Immunization in Mice

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Pharmaceutics 2023, 15(5), 1412; https://doi.org/10.3390/pharmaceutics15051412 - 05 May 2023

Viewed by 655

Abstract

Neutralizing antibodies (nAbs), the popular antiviral drugs used for the treatment of COVID-19, are effective in reducing viral load and hospitalization. Currently, most nAbs are screened from convalescent or vaccinated individuals through single B-cell sequencing which requires cutting-edge facilities. Moreover, owing to the rapid mutation of SARS-CoV-2, some approved nAbs are no longer effective. In the present study, we designed a new approach to acquiring broadly neutralizing antibodies (bnAbs) from mRNA-vaccinated mice. Using the flexibility and speed of mRNA vaccine preparation, we designed a chimeric mRNA vaccine and sequential immunization strategies to acquire bnAbs in mice within a short period. By comparing different vaccination orders, we found that the initially administered vaccine had a greater effect on the neutralizing potency of mouse sera. Ultimately, we screened a strain of bnAb that neutralized wild-type, Beta, and Delta SARS-CoV-2 pseudoviruses. We synthesized the mRNAs of the heavy and light chains of this antibody and verified its neutralizing potency. This study developed a new strategy to screen for bnAbs in mRNA-vaccinated mice and identified a more effective immunization strategy for inducing bnAbs, providing valuable insights for future antibody drug development. Full article

(This article belongs to the Special Issue Recent Advances in Therapeutic Antibody)

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Open AccessArticle

Adalimumab Serum Concentrations, Clinical and Endoscopic Disease Activity in Crohn’s Disease: A Cross-Sectional Multicentric Latin American Study

Letícia Rodrigues de Souza

Daniela Oliveira Magro

Fábio Vieira Teixeira

Rogério Serafim Parra

Eron Fábio Miranda

Omar Féres

Rogério Saad-Hossne

Giedre Soares Prates Herrerias

Renato Mitsunori Nisihara

Claudio Saddy Rodrigues Coy

Ligia Yukie Sassaki

and

Paulo Gustavo Kotze

Pharmaceutics 2023, 15(2), 586; https://doi.org/10.3390/pharmaceutics15020586 - 09 Feb 2023

Viewed by 559

Abstract

Despite some variability in ideal serum Adalimumab (ADA) concentrations, there is increasing evidence that higher concentrations of anti-TNF-α agents can be associated with sustained efficacy, and low or undetectable levels may lead to loss of response. This study aims to correlate serum ADA concentrations with clinical and endoscopic activity in patients with Crohn’s disease (CD). A cross-sectional and multicentric study was performed with patients with CD, who used ADA for at least 24 weeks. Patients were allocated into groups according to the presence of clinical or endoscopic disease activity. Serum ADA concentrations were measured and compared between groups. Overall, 89 patients were included. A total of 27 patients had clinically active CD and 62 were in clinical remission. Forty patients had endoscopic disease activity and 49 were in endoscopic remission. The mean serum ADA concentration was 10.2 μg/mL in patients with clinically active CD and 14.3 μg/mL in patients in clinical remission (p = 0.395). The mean serum ADA concentration in patients with endoscopic activity was 11.3 μg/mL as compared to 14.5 μg/mL in those with endoscopic remission (p = 0.566). There was no difference between serum ADA concentrations regarding clinical or endoscopic activity in CD, as compared to patients in remission Full article

(This article belongs to the Special Issue Recent Advances in Therapeutic Antibody)

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Open AccessArticle

An Engineered IFNγ-Antibody Fusion Protein with Improved Tumor-Homing Properties

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Pharmaceutics 2023, 15(2), 377; https://doi.org/10.3390/pharmaceutics15020377 - 22 Jan 2023

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Abstract

Interferon-gamma (IFNγ) is one of the central cytokines produced by the innate and adaptive immune systems. IFNγ directly favors tumor growth control by enhancing the immunogenicity of tumor cells, induces IP-10 secretion facilitating (CXCR3+) immune cell infiltration, and can prime macrophages to an M1-like phenotype inducing proinflammatory cytokine release. We had previously reported that the targeted delivery of IFNγ to neoplastic lesions may be limited by the trapping of IFNγ-based products by cognate receptors found in different organs. Here we describe a novel fusion protein consisting of the L19 antibody, specific to the alternatively spliced extra-domain B of fibronectin (EDB), fused to a variant of IFNγ with reduced affinity to its cognate receptor. The product (named L19-IFNγ KRG) selectively localized to tumors in mice, showed favorable pharmacokinetic profiles in monkeys and regained biological activity upon antigen binding. The fusion protein was investigated in two murine models of cancer, both as monotherapy and in combination with therapeutic modalities which are frequently used for cancer therapy. L19-IFNγ KRG induced tumor growth retardation and increased the intratumoral concentration of T cells and NK cells in combination with anti-PD-1. Full article

(This article belongs to the Special Issue Recent Advances in Therapeutic Antibody)

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Open AccessArticle

Antitumor Activity of an Anti-EGFR/HER2 Bispecific Antibody in a Mouse Xenograft Model of Canine Osteosarcoma

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Pharmaceutics 2022, 14(11), 2494; https://doi.org/10.3390/pharmaceutics14112494 - 17 Nov 2022

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Abstract

The overexpression of epidermal growth factor receptors (EGFRs) has been reported in various human tumors, including breast, gastric, lung, colorectal, and pancreatic cancers. Humanized anti-EGFR and anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibodies (mAbs) have been shown to improve patients’ survival. Canine tumors resemble human tumors in the initiation and progression. We previously established a defucosylated mouse-dog chimeric anti-EGFR mAb (E134Bf) and a mouse-dog chimeric anti-HER2 mAb (H77Bf), which exerted antitumor activities in canine tumor xenograft models. Here, we produced E134Bf antibody fused to H77Bf single chain Fv at the light chains (E134Bf-H77scFv). The bispecific E134Bf-H77scFv recognized dog EGFR (dEGFR) and dog HER2 (dHER2)-overexpressed Chinese hamster ovary-K1 cells by flow cytometry. E134Bf-H77scFv also reacted with dEGFR/dHER2-positive canine osteosarcoma D-17 cells, and possesses a high binding-affinity (K_D: 1.3 × 10⁻⁹ M). Furthermore, E134Bf-H77scFv exerted antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against D-17 cells in the presence of canine mononuclear cells and complement, respectively. Moreover, administration of E134Bf-H77scFv suppressed the development of D-17 xenograft tumor in mice early compared with the control dog IgG, E134Bf and H77Bf alone. These results indicate that E134Bf-H77scFv exerts antitumor activities against dEGFR/dHER2-positive canine tumors, and could be a valuable treatment regimen for canine tumors. Full article

(This article belongs to the Special Issue Recent Advances in Therapeutic Antibody)

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Open AccessReview

Advances in Antibody-Based Therapeutics for Cerebral Ischemia

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Pharmaceutics 2023, 15(1), 145; https://doi.org/10.3390/pharmaceutics15010145 - 31 Dec 2022

Cited by 1 | Viewed by 1108

Abstract

Cerebral ischemia is an acute disorder characterized by an abrupt reduction in blood flow that results in immediate deprivation of both glucose and oxygen. The main types of cerebral ischemia are ischemic and hemorrhagic stroke. When a stroke occurs, several signaling pathways are activated, comprising necrosis, apoptosis, and autophagy as well as glial activation and white matter injury, which leads to neuronal cell death. Current treatments for strokes include challenging mechanical thrombectomy or tissue plasminogen activator, which increase the danger of cerebral bleeding, brain edema, and cerebral damage, limiting their usage in clinical settings. Monoclonal antibody therapy has proven to be effective and safe in the treatment of a variety of neurological disorders. In contrast, the evidence for stroke therapy is minimal. Recently, Clone MTS510 antibody targeting toll-like receptor-4 (TLR4) protein, ASC06-IgG1 antibody targeting acid sensing ion channel-1a (ASIC1a) protein, Anti-GluN1 antibodies targeting N-methyl-D-aspartate (NMDA) receptor associated calcium influx, GSK249320 antibody targeting myelin-associated glycoprotein (MAG), anti-High Mobility Group Box-1 antibody targeting high mobility group box-1 (HMGB1) are currently under clinical trials for cerebral ischemia treatment. In this article, we review the current antibody-based pharmaceuticals for neurological diseases, the use of antibody drugs in stroke, strategies to improve the efficacy of antibody therapeutics in cerebral ischemia, and the recent advancement of antibody drugs in clinical practice. Overall, we highlight the need of enhancing blood–brain barrier (BBB) penetration for the improvement of antibody-based therapeutics in the brain, which could greatly enhance the antibody medications for cerebral ischemia in clinical practice. Full article

(This article belongs to the Special Issue Recent Advances in Therapeutic Antibody)

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