ArticlemAbs
Rational engineering of antibody therapeutics targeting multiple oncogene pathways.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed.
- Article
- Molecular Mechanism of HER2 Rapid Internalization and Redirected Trafficking Induced by Anti-HER2 Biparatopic Antibody.Antibodies (Basel, Switzerland) · 2020Article
- Enhancing natural killer cell function with gp41-targeting bispecific antibodies to combat HIV infection.AIDS (London, England) · 2020Article
- Dual targeting of IGF-1R and ErbB3 as a potential therapeutic regimen for ovarian cancer.Scientific reports · 2019Article
- Recombinant Antibodies to Arm Cytotoxic Lymphocytes in Cancer Immunotherapy.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2017Review
- Enhanced tumor-targeting selectivity by modulating bispecific antibody binding affinity and format valence.Scientific reports · 2017Article
- Emerging Strategies for Developing Next-Generation Protein Therapeutics for Cancer Treatment.Trends in pharmacological sciences · 2016Review
- Article
- Selective Targeting of Cells via Bispecific Molecules That Exploit Coexpression of Two Intracellular Proteins.ACS chemical biology · 2015Article
- Efficient production of single-chain fragment variable-based N-terminal trimerbodies in Pichia pastoris.Microbial cell factories · 2014Article
- Using network biology to bridge pharmacokinetics and pharmacodynamics in oncology.CPT: pharmacometrics & systems pharmacology · 2013Article
- Strengthening relationships: amyloids create adhesion nanodomains in yeasts.Trends in microbiology · 2012Article
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- Article
- Review
- Article
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Monoclonal antibodies have significantly advanced our ability to treat cancer, yet clinical studies have shown that many patients do not adequately respond to monospecific therapy. This is in part due to the multifactorial nature of the disease, where tumors rely on multiple and often redundant pathways for proliferation. Bi- or multi- specific antibodies capable of blocking multiple growth and survival pathways at once have a potential to better meet the challenge of blocking cancer growth, and indeed many of them are advancing in clinical development. ( 1) However, bispecific antibodies present significant design challenges mostly due to the increased number of variables to consider. In this perspective we describe an innovative integrated approach to the discovery of bispecific antibodies with optimal molecular properties, such as affinity, avidity, molecular format and stability. This approach combines simulations of potential inhibitors using mechanistic models of the disease-relevant biological system to reveal optimal inhibitor characteristics with antibody engineering techniques that yield manufacturable therapeutics with robust pharmaceutical properties. We illustrate how challenges of meeting the optimal design criteria and chemistry, manufacturing and control concerns can be addressed simultaneously in the context of an accelerated therapeutic design cycle. Finally, to demonstrate how this rational approach can be applied, we present a case study where the insights from mechanistic modeling were used to guide the engineering of an IgG-like bispecific antibody.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.