Crystallographic approaches to study the interaction modes of PD-1- and CTLA-4-blocking antibodies.
Methods Enzymol
; 629: 383-399, 2019.
Article
em En
| MEDLINE
| ID: mdl-31727250
ABSTRACT
The programmed death 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) are negative regulators of T-cell immune function. Removal of these "brakes" in T cells results in increased activation of the immune system and controlling and eradicating tumor. The development of immune checkpoint inhibitors (ICIs) is a revolutionary milestone in tumor immunotherapy. Obtaining the atomic structure of the human immune checkpoint receptor/ICI therapeutic antibody complex is essential for understanding its inhibition mechanism and the rational design of improved biotherapeutics. In this chapter, we describe the methods for efficient production of extracellular domain of human immune checkpoint receptors and Fv fragments of ICI therapeutic antibodies in milligram quantities sufficient for structural studies, taking examples of the PD-1/pembrolizumab Fv and CTLA-4-ipilimumab Fv complexes.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Difração de Raios X
/
Região Variável de Imunoglobulina
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Antineoplásicos Imunológicos
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Neoplasias
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Methods Enzymol
Ano de publicação:
2019
Tipo de documento:
Article
País de publicação:
EEUU
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ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA