Next Article in Journal
Gradual and Discrete Ontogenetic Shifts in Rattlesnake Venom Composition and Assessment of Hormonal and Ecological Correlates
Previous Article in Journal
Prevalence, Genotypic and Phenotypic Characterization and Antibiotic Resistance Profile of Clostridium perfringens Type A and D Isolated from Feces of Sheep (Ovis aries) and Goats (Capra hircus) in Punjab, Pakistan
Previous Article in Special Issue
Novel Binding Mechanisms of Fusion Broad Range Anti-Infective Protein Ricin A Chain Mutant-Pokeweed Antiviral Protein 1 (RTAM-PAP1) against SARS-CoV-2 Key Proteins in Silico
Open AccessReview

Immunotoxin Screening System: A Rapid and Direct Approach to Obtain Functional Antibodies with Internalization Capacities

1
Research Institute for Diseases of Old Age, Juntendo University School of Medicine, Tokyo 113-8421, Japan
2
Department of Neurology, Juntendo University School of Medicine, Tokyo 113-8421, Japan
3
Department of Research for Parkinson’s Disease, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan
4
Neurodegenerative Disorders Collaborative Laboratory, RIKEN Center for Brain Science, Saitama 351-0198, Japan
*
Author to whom correspondence should be addressed.
Toxins 2020, 12(10), 658; https://doi.org/10.3390/toxins12100658
Received: 30 September 2020 / Revised: 13 October 2020 / Accepted: 14 October 2020 / Published: 15 October 2020
(This article belongs to the Special Issue Toxin and Immunotoxin Based Therapeutic Approaches)
Toxins, while harmful and potentially lethal, have been engineered to develop potent therapeutics including cytotoxins and immunotoxins (ITs), which are modalities with highly selective targeting capabilities. Currently, three cytotoxins and IT are FDA-approved for treatment of multiple forms of hematological cancer, and additional ITs are tested in the clinical trials or at the preclinical level. For next generation of ITs, as well as antibody-mediated drug delivery systems, specific targeting by monoclonal antibodies is critical to enhance efficacies and reduce side effects, and this methodological field remains open to discover potent therapeutic monoclonal antibodies. Here, we describe our application of engineered toxin termed a cell-based IT screening system. This unique screening strategy offers the following advantages: (1) identification of monoclonal antibodies that recognize cell-surface molecules, (2) selection of the antibodies that are internalized into the cells, (3) selection of the antibodies that induce cytotoxicity since they are linked with toxins, and (4) determination of state-specific activities of the antibodies by differential screening under multiple experimental conditions. Since the functional monoclonal antibodies with internalization capacities have been identified successfully, we have pursued their subsequent modifications beyond antibody drug conjugates, resulting in development of immunoliposomes. Collectively, this screening system by using engineered toxin is a versatile platform, which enables straight-forward and rapid selection for discovery of novel functional antibodies. View Full-Text
Keywords: monoclonal antibody; immunotoxin; antibody drug conjugate; immunoliposome; drug delivery; diphtheria toxin; DT3C monoclonal antibody; immunotoxin; antibody drug conjugate; immunoliposome; drug delivery; diphtheria toxin; DT3C
Show Figures

Figure 1

MDPI and ACS Style

Hamamichi, S.; Fukuhara, T.; Hattori, N. Immunotoxin Screening System: A Rapid and Direct Approach to Obtain Functional Antibodies with Internalization Capacities. Toxins 2020, 12, 658.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop