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Perspective: Designing T-Cell Engagers With Better Therapeutic Windows.
Vafa, Omid; Trinklein, Nathan D.
Afiliação
  • Vafa O; Teneobio, Inc., Newark, CA, United States.
  • Trinklein ND; Teneobio, Inc., Newark, CA, United States.
Front Oncol ; 10: 446, 2020.
Article em En | MEDLINE | ID: mdl-32351885
This perspective highlights the history and challenges of developing CD3-based bispecific T-cell engagers (TCEs) as cancer therapeutics as well as considerations and potential strategies for designing the next generation TCE molecules. The goal of this article is to raise awareness of natural T-cell biology and how to best harness the tumor cell killing capacity of cytotoxic T-cells with TCEs. In light of 30 years of concerted efforts to advance TCEs in early clinical development, many of the first-generation bispecific antibodies have exhibited lackluster safety, efficacy, and manufacturability profiles. As of January 2020, blinatumomab remains the only approved TCE. Many of the current set-backs in early clinical trials implicate the high-affinity CD3 binding domains employed and the respective bispecific platforms as potential culprits. The underlying conviction of the authors is that by taking corrective measures, TCEs can transform cancer therapy. Through openness, transparency, and much needed feedback from ongoing clinical studies, the field can continuously improve the design and effectiveness of next generation T-cell redirecting therapeutics.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos