It has been more than three decades since the first monoclonal antibody was approved by the United States Food and Drug Administration (US FDA) in 1986, and during this time, antibody engineering has dramatically evolved. Current antibody drugs have increasingly fewer adverse effects due to their high specificity. As a result, therapeutic antibodies have become the predominant class of new drugs developed in recent years. Over the past five years, antibodies have become the best-selling drugs in the pharmaceutical market, and in 2018, eight of the top ten bestselling drugs worldwide were biologics. The global therapeutic monoclonal antibody market was valued at approximately US$115.2 billion in 2018 and is expected to generate revenue of $150 billion by the end of 2019 and $300 billion by 2025. Thus, the market for therapeutic antibody drugs has experienced explosive growth as new drugs have been approved for treating various human diseases, including many cancers, autoimmune, metabolic and infectious diseases. As of December 2019, 79 therapeutic mAbs have been approved by the US FDA, but there is still significant growth potential. This review summarizes the latest market trends and outlines the preeminent antibody engineering technologies used in the development of therapeutic antibody drugs, such as humanization of monoclonal antibodies, phage display, the human antibody mouse, single B cell antibody technology, and affinity maturation. Finally, future applications and perspectives are also discussed.

/pdf/development-of-therapeutic-antibodies-for-the-treatment-of-4g7fs3ndpf.pdf

Development of therapeutic antibodies for the treatment of diseases

The term bispecific antibody (bsAb) is used to describe a large family of molecules designed to recognize two different epitopes or antigens. BsAbs come in many formats, ranging from relatively small proteins, merely consisting of two linked antigen-binding fragments, to large immunoglobulin G (IgG)-like molecules with additional domains attached. An attractive bsAb feature is their potential for novel functionalities - that is, activities that do not exist in mixtures of the parental or reference antibodies. In these so-called obligate bsAbs, the physical linkage of the two binding specificities creates a dependency that can be temporal, with binding events occurring sequentially, or spatial, with binding events occurring simultaneously, such as in linking an effector to a target cell. To date, more than 20 different commercialized technology platforms are available for bsAb creation and development, 2 bsAbs are marketed and over 85 are in clinical development. Here, we review the current bsAb landscape from a mechanistic perspective, including a comprehensive overview of the pipeline.

Bispecific antibodies: a mechanistic review of the pipeline.

During the past two decades we have seen a phenomenal evolution of bispecific antibodies for therapeutic applications. The ‘zoo’ of bispecific antibodies is populated by many different species, comprising around 100 different formats, including small molecules composed solely of the antigen-binding sites of two antibodies, molecules with an IgG structure, and large complex molecules composed of different antigen-binding moieties often combined with dimerization modules. The application of sophisticated molecular design and genetic engineering has solved many of the technical problems associated with the formation of bispecific antibodies such as stability, solubility and other parameters that confer drug properties. These parameters may be summarized under the term ‘developability’. In addition, different ‘target product profiles’, i.e., desired features of the bispecific antibody to be generated, mandates the need for access to a diverse panel of formats. These may vary in size, arrangement, vale...

https://www.tandfonline.com/doi/pdf/10.1080/19420862.2016.1268307

The making of bispecific antibodies

Antibody therapeutics are now established as a major drug class. Here, Carter and Lazar comprehensively discuss current and emerging platforms and technologies for antibody therapeutics, with an emphasis on approaches that could extend their therapeutic applications, including antibody–drug conjugates, bispecific antibodies and antibody engineering to enable more effective delivery.

Next generation antibody drugs: pursuit of the 'high-hanging fruit'.

Alternative molecular formats and therapeutic applications for bispecific antibodies.

The in vitro and in vivo pharmacologic assessment of ABP 980 similarity to its reference product is intended to compare the activity of ABP 980 and trastuzumab and support the overall conclusion of similarity based on a comprehensive analytical and functional evaluation. This work complements the primary assessment of functional similarity with additional in vitro assays, binding studies, and non-clinical studies including human epidermal growth factor receptor-2 (HER2) kinetic binding, HER2 signaling, HER2 internalization, synergy with docetaxel chemotherapy, FcγR kinetic binding, primary natural killer and monocyte cell binding, antibody-dependent cellular phagocytosis activity, in vivo xenograft studies, and toxicokinetic parameters. The results contribute to the totality of evidence with respect to functional similarity and support that ABP 980 is similar to trastuzumab in all primary and secondary mechanisms of action. These results also support the scientific justification of extrapolation to all approved indications of trastuzumab given the established functional similarity of the two products and the same mechanisms of action across all conditions of use.

/pdf/functional-and-nonclinical-similarity-of-abp-980-a-5by4gjq4ff.pdf

Functional and Nonclinical Similarity of ABP 980, a Biosimilar of Trastuzumab

Analytical and functional similarity of biosimilar ABP 798 with rituximab reference product.

Functional Similarity of Proposed Biosimilar ABP 798 with Rituximab

ABP 501: Matching the Critical Functions of Adalimumab

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC

Introduction: Angiogenesis is required for tumor growth. Vascular endothelial growth factor (VEGF) and its receptors (VEGFR) play a critical role in the development of neovascularization. Motesanib is an orally administered small-molecule inhibitor of angiogenesis with direct antitumor activity, targeting VEGFR1, 2, and 3; platelet-derived growth factor receptor (PDGFR), and stem cell factor receptor (c-kit). In this study, we examined the effects of motesanib in preclinical models of human non-small cell lung cancer (NSCLC), both as a single agent and in combination with docetaxel or cisplatin.

Methods: The ability of motesanib to inhibit the growth of NSCLC cell lines in vitro was assessed using the ATPlite cell viability assay. Five human NSCLC cell lines were evaluated, including A549 (adenocarcinoma), Calu-6 (anaplastic carcinoma), NCI-H358 (bronchioalveolar carcinoma), NCI-H1299 (large cell carcinoma) and NCI-H1650 (adenocarcinoma). To determine in vivo efficacy, mice bearing established xenografts were treated orally with motesanib BID or QD at doses ranging from 7.5 to 75 mg/kg. For combination experiments, cisplatin (4 or 5 mg/kg) or docetaxel (5, 15 or 30 mg/kg) administered IP once weekly were given with motesanib. Tumors were collected for assessment of blood vessel area (anti-CD31 staining) and viable tumor area (hematoxylin staining). Tumor burden was calculated as the viable fraction multiplied by the respective terminal tumor weight.

Results: Motesanib had no effect on the in vitro growth of any of the lung cancer cell lines tested (IC50 >5 µM). In contrast, treatment with motesanib in vivo resulted in a dose-dependent inhibition of tumor growth in all five lung cancer models. In combination studies, treatment with motesanib and cisplatin significantly enhanced (p <0.05) the antitumor activity in the NCI-H358, NCI-H1650, and Calu-6 xenograft models. Treatment with motesanib in combination with docetaxel significantly enhanced (p <0.05) the anti-tumor activity in the Calu-6 and A549 models, compared with either single agent alone. All treatments were well tolerated. The factors responsible for the differential sensitivity of these tumors to motesanib are currently being explored. Histological analyses of NCI-H358 tumors revealed a reduction in blood vessel area after treatment with motesanib alone and in combination with cisplatin, as well as a significant decrease in viable tumor burden after combination therapy (p <0.05). Together, these data suggest that motesanib prevented tumor growth by inhibiting angiogenesis, and combination of motesanib with chemotherapy resulted in a significantly enhanced reduction in tumor growth.

Conclusion: The antitumor activity of motesanib in multiple preclinical models of NSCLC supports development of this antiangiogenic agent for the management of NSCLC in combination with standard of care chemotherapy.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1380.

Abstract 1380: Antitumor activity of motesanib alone and in combination with chemotherapy in xenograft models of human non-small cell lung cancer

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Heather Sweet

Author Tools

Chat about Author