Current strategies in antibody engineering: Fc engineering and pH-dependent antigen binding, bispecific antibodies and antibody drug conjugates

2012 ◽  
Vol 7 (12) ◽  
pp. 1444-1450 ◽  
Author(s):  
Karen J. Vincent ◽  
Mauro Zurini
Keyword(s):  
Antibody Engineering ◽  
Bispecific Antibodies ◽  
Antigen Binding ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Ph Dependent ◽  
Antibody Drug

scholarly journals Importance and Considerations of Antibody Engineering in Antibody-Drug Conjugates Development from a Clinical Pharmacologist’s Perspective

Antibodies ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 30
Author(s):  
Andrew T. Lucas ◽  
Amber Moody ◽  
Allison N. Schorzman ◽  
William C. Zamboni
Keyword(s):  
Immune System ◽  
Market Value ◽  
Therapeutic Index ◽  
Drug Carriers ◽  
Antibody Engineering ◽  
Antibody Drug Conjugates ◽  
Success Stories ◽  
Drug Conjugates ◽  
Early Success ◽  
Antibody Drug

Antibody-drug conjugates (ADCs) appear to be in a developmental boom, with five FDA approvals in the last two years and a projected market value of over $4 billion by 2024. Major advancements in the engineering of these novel cytotoxic drug carriers have provided a few early success stories. Although the use of these immunoconjugate agents are still in their infancy, valuable lessons in the engineering of these agents have been learned from both preclinical and clinical failures. It is essential to appreciate how the various mechanisms used to engineer changes in ADCs can alter the complex pharmacology of these agents and allow the ADCs to navigate the modern-day therapeutic challenges within oncology. This review provides a global overview of ADC characteristics which can be engineered to alter the interaction with the immune system, pharmacokinetic and pharmacodynamic profiles, and therapeutic index of ADCs. In addition, this review will highlight some of the engineering approaches being explored in the creation of the next generation of ADCs.

Bispecific Antibodies and Antibody–Drug Conjugates (ADCs) Bridging HER2 and Prolactin Receptor Improve Efficacy of HER2 ADCs

2017 ◽  
Vol 16 (4) ◽  
pp. 681-693 ◽  
Author(s):  
Julian Andreev ◽  
Nithya Thambi ◽  
Andres E. Perez Bay ◽  
Frank Delfino ◽  
Joel Martin ◽  
...  
Keyword(s):  
Prolactin Receptor ◽  
Bispecific Antibodies ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Antibody Drug

Site-Specific Trastuzumab Maytansinoid Antibody–Drug Conjugates with Improved Therapeutic Activity through Linker and Antibody Engineering

2014 ◽  
Vol 57 (19) ◽  
pp. 7890-7899 ◽  
Author(s):  
Thomas H. Pillow ◽  
Janet Tien ◽  
Kathryn L. Parsons-Reponte ◽  
Sunil Bhakta ◽  
Hao Li ◽  
...  
Keyword(s):  
Antibody Engineering ◽  
Therapeutic Activity ◽  
Site Specific ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Antibody Drug

Monoclonal Antibodies, Bispecific Antibodies and Antibody-Drug Conjugates in Oncohematology

2020 ◽  
Vol 15 (4) ◽  
pp. 272-292
Author(s):  
Romeo G. Mihăilă
Keyword(s):  
Monoclonal Antibodies ◽  
Target Cell ◽  
Residual Disease ◽  
Standard Of Care ◽  
Bispecific Antibodies ◽  
Target Antigen ◽  
Target Cells ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Antibody Drug

Background: The therapeutic outcomes and the prognosis of patients with various hematologic malignancies are not always ideal with the current standard of care. Objective: The aim of this study is to analyze the results of the use of monoclonal antibodies, bispecific antibodies and antibody-drug conjugates for the therapy of malignant hemopathies. Methods: A mini-review was achieved using the articles published in Web of Science and PubMed between January 2017 and January 2020 and the new patents were made in this field. Results: Naked monoclonal antibodies have improved the therapeutic results obtained with standard of care, but they also have side effects and the use of some of them can lead to the loss of the target antigen through trogocytosis, which explains the resistance that occurs during therapy. The results obtained with naked monoclonal antibodies have been improved by a better monoclonal antibody preparation, the use of bispecific antibodies (against two antigens on the target cell surface or by binding both surface antigen on target cells and T-cell receptor complex, followed by cytotoxic T-lymphocytes activation and subsequent cytolysis of the target cell), the use of monoclonal or bispecific constructs in frontline regimens, combining immunotherapy with chemotherapy, including through the use of antibody-drug conjugates (which provides a targeted release of a chemotherapeutic agent). Conclusion: Immunotherapy and immuno-chemotherapy have improved the outcome of the patients with malignant hemopathies through a targeted, personalized therapy, with reduced systemic toxicity, which in some cases can even induce deep complete remissions, including minimal residual disease negativity.

scholarly journals Bispecific Antibodies and Antibody–Drug Conjugates for Cancer Therapy: Technological Considerations

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 360 ◽  
Author(s):  
Hyunbo Shim
Keyword(s):  
Therapeutic Antibody ◽  
Bispecific Antibodies ◽  
Target Antigen ◽  
Antibody Drug Conjugates ◽  
Medical Needs ◽  
Drug Conjugates ◽  
Recent Developments ◽  
Technological Developments ◽  
Approved Drugs ◽  
Antibody Drug

The ability of monoclonal antibodies to specifically bind a target antigen and neutralize or stimulate its activity is the basis for the rapid growth and development of the therapeutic antibody field. In recent years, traditional immunoglobulin antibodies have been further engineered for better efficacy and safety, and technological developments in the field enabled the design and production of engineered antibodies capable of mediating therapeutic functions hitherto unattainable by conventional antibody formats. Representative of this newer generation of therapeutic antibody formats are bispecific antibodies and antibody–drug conjugates, each with several approved drugs and dozens more in the clinical development phase. In this review, the technological principles and challenges of bispecific antibodies and antibody–drug conjugates are discussed, with emphasis on clinically validated formats but also including recent developments in the fields, many of which are expected to significantly augment the current therapeutic arsenal against cancer and other diseases with unmet medical needs.

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