Sacituzumab govitecan, a novel, third-generation, antibody-drug conjugate (ADC) for cancer therapy.
Expert Opin Biol Ther
; 20(8): 871-885, 2020 08.
Article
en En
| MEDLINE
| ID: mdl-32301634
ABSTRACT
INTRODUCTION:
We describe a new, third-generation of antibody-drug conjugates (ADCs) having a high drug payload against topoisomerase I, important for DNA function, and targeting selective tumor antigens, predominantly TROP-2. AREAS COVERED The historical development of ADCs is reviewed before presenting the current line of improved, third-generation ADCs targeting topoisomerase I, thus affecting DNA and causing double-stranded DNA breaks. Emphasis is given to explaining why sacituzumab govitecan represents a paradigm change in ADCs by achieving a high therapeutic index due to its novel target, TROP-2, an internalizing antigen/antibody, proprietary linker chemistry, and high drug payload, resulting in a high tumor concentration of the drug given in repeated doses with acceptable tolerability, particularly evidencing a lower percentage of 'late' diarrhea than its prodrug, irinotecan. PubMed was used for the primary search conducted. EXPERT OPINION The properties and clinical results of third-generation ADCs, based on sacituzumab govitecan, are discussed, including prospects for future applications, particularly combination therapies with PARP inhibitors and immune checkpoint inhibitors. Since one topoisomerase I ADC has just received regulatory approval for HER2+ breast cancer, and sacituzumab govitecan is under FDA review for accelerated approval in the therapy of triple-negative breast cancer, the prospects for these novel ADCs are discussed.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Camptotecina
/
Inmunoconjugados
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Anticuerpos Monoclonales Humanizados
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Neoplasias
Límite:
Humans
Idioma:
En
Revista:
Expert Opin Biol Ther
Asunto de la revista:
BIOLOGIA
/
TERAPEUTICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos