Inside Labs
Inside Labs
Monoclonal Antibody CT-P59: Another Silver Bullet Against Novel Coronavirus
Update 21.06.2022
Researchers in Korea report a novel monoclonal antibody called CT-P59 against SARS-CoV-2, offering hope for effective therapy and prophylaxis
As the
COVID-19 pandemic rages on across the world, researchers have been hard at work
to identify therapeutics that can effectively check SARS-CoV-2, the disease-causing
pathogen. One such attempt by a group of researchers in Korea has yielded the
monoclonal antibody CT-P59, which effectively neutralizes SARS-CoV-2, according
to a study published in Nature Communications, offering a potential new
therapy against COVID-19.
Korean researchers have identified an
effective monoclonal antibody, CT-P59, against the novel coronavirus
Image courtesy: Sutterstock
The ongoing COVID-19 pandemic has posed a serious challenge for the medical
community and the healthcare sector in most countries. Despite research going
on at war footing on vaccines and therapeutics across the globe, the available
treatment options are limited, both in diversity and effectiveness. In this
regard, convalescent plasma therapy with antibodies that neutralize the virus and
obtained from patients recovering from COVID-19 is under investigation.
The therapy involves treating patients with a concoction of antibodies that
bind to the virus, inhibiting it, thereby alleviating the severe symptoms of
the disease. However, this strategy is plagued by shortcomings like scalability
issues and lot-to-lot variations. To avoid these disadvantages, researchers have
been investigating specific antibodies that will have the most effect against
the virus.
According to a recent study
published in Nature Communications, a group of researchers in Korea have now succeeded in identifying an
effective neutralizing antibody against SARS-CoV-2, called the CT-P59. This inventive
work was accomplished under the collaboration of the governmental institute, National Institute of Health, and private agencies,
and was supported by a Korea National Institute of Health fund
(2020-ER5311-00,2020-ER5323-00, 2019-NI-077-01, 2019-NG-044-01).
In the current study, the researchers identified CT-P59 from an antibody library (collection of antibodies that develop in the body in response to an antigenic stimulus), constructed from peripheral blood mononuclear cells of a patient recovering from COVID-19. After identifying CT-P59, they enumerated these as monoclonal antibodies (mAb) in the laboratory, with selective specificity for the viral antigen, eventually redesigning them into fully human antibodies. The therapeutic efficacy of these mAbs was evaluated in animal models of COVID-19, including hamsters, ferrets, and rhesus monkeys. The results were promising, which encouraged the researchers to progress to the next step.
The researchers found that CT-P59 potentially neutralizes SARS-CoV-2
isolates without causing antibody-dependent enhancement, in which there is an immune
system-mediated aggravation of the disease in patients. To determine the
precise mechanism by which CT-P59 achieves this, they analyzed the interaction
of the antibody with the virus using X-ray crystallography that ‘stops’ the
biomolecular event at the point of inquiry.
The researchers observed that CT-P59 bound to the receptor binding domain
(RBD) of the viral surface spike protein blocks substantial areas of the target
host cellular receptor, angiotensin converting enzyme 2 (ACE2), which
prevents the virus from interacting with the target host cell. As a
spokesperson for the team explains,, “Complex crystal structure of the
virus-host biomolecular interaction shows that CT-P59 blocks interaction
regions of RBD for ACE2 receptor with an orientation that is notably different
from previously reported RBD-targeting mAb.” Moreover, CT-P59 does not bind
to the frequently mutated amino acid residues at position 367, 436, or 364 of
the RBD; this suggests the antibody can effectively neutralize naturally
occurring mutated forms of the virus. In addition, the researchers found that
CT-P59 treatment in COVID-19 animal models not only substantially reduced viral
titers, but also alleviated the clinical symptoms. A trove of good news in the
middle of the ongoing COVID-19 ‘battle’, indeed!
The research team is confident about the potential of this innovative study:
“CT-P59 is a promising treatment for COVID-19 patients as well as a
prophylactic option. The effectiveness and safety of CT-P59 have been proven in
phase I and II clinical trials; phase III clinical trials are currently
underway in South Korea and other countries.”
For a COVID-19-battered world, nothing could be a more
welcome news!
Reference
Authors
Jong-In Kim, Pankyeom Kim, Jin Soo Bae, Eun Yeong Shim, Min Seob Lee, Man Su Kim, Hanmi Noh, Geun-Soo Park,
Jae Sang Park, Dain Son, Yongjin An, Jeong No Lee, Ki-Sung Kwon, Joo-Yeon Lee, Hansaem Lee, Jeong-Sun Yang,
Kyung-Chang Kim, Sung Soon Kim, Hye-Min Woo, Jun-Won Kim, Man-Seong Park, Kwang-Min Yu, Se-Mi Kim,
Eun-Ha Kim, Su-Jin Park, Seong Tae Jeong, Chi Ho Yu, Youngjo Song, Se Hun Gu, Hanseul Oh, Bon-Sang Koo,
Jung Joo Hong, Choong-Min Ryu, Wan Beom Park, Myoung-don Oh, Young Ki Choi, and Soo-Young Lee
Title of original paper
Journal Nature Communications
DOI https://doi.org/10.1038/s41467-020-20602-5
Affiliations Biotechnology Research Institute, Celltrion Inc., Incheon;
College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju;
Pohang Accelerator Laboratory, Pohang University of Science and Technology, Pohang, Kyungbuk;
Center for Infectious Diseases Research, Korea National Institute of Health, Korea Centers for Disease Control and
Prevention Agency, Cheongju;
Department of Microbiology and Institute for Viral Diseases, College of Medicine, Korea University, Seoul;
The 4th R&D Institute, Agency for Defense Development, Yuseong, Daejeon;
National Primate Research Centre, Korea Research Institute of Bioscience and Biotechnology, Cheongju;
Infectious Disease Research Centre, Korea Research Institute of Bioscience and Biotechnology, Daejeon;
Department of Internal Medicine, Seoul National University College of Medicine, Seoul;
and Division of Applied Life Science and Research Institute of Life Sciences, Gyeongsang National University, Jinju
About
National Institute of Health in Korea
The
Korea National Institute of Health (KNIH), one of the major operating
components of the Ministry of Health and Welfare, leads the nation’s medical
research. Over the past seven decades, the KNIH has made unwavering efforts to
enhance the public’s health and innovate biomedical research. The KNIH seeks to
eradicate diseases and make people healthier. The KNIH establishes a scientific
basis and evidence underlying health policy as well as provides national
research infrastructures. We also promote public health research. To this end,
we make efforts to enrich a health research environment by granting funds to
research projects and keeping our resources, data, and facilities more open and
accessible to researchers.
Website: http://www.nih.go.kr/eng/
About the Division of
Emerging Virus and Vector Research
The division of
emerging virus and vector research belongs to Korea National Institute of
infectious diseases, Korea National Institute of Health, Korea Disease Control
and Prevention Agency. This division is conducting research on the development
of therapeutics, diagnostics, and evaluation systems for emerging viral
diseases such as COVID-19, MERS, etc. Moreover, the team is also working to establish
a platform for control technology to respond to high risk infections such as
viral hemorrhagic fevers, Nipah virus infection, etc. Also, they are facilitating
research networks and advanced infrastructure through various national and
international collaboration to combat the COVID-19 pandemic and prepare the
control system for disease X.