Structure-Activity Relationships of Antibody-Drug Conjugates: A Systematic Review of Chemistry on the Trastuzumab Scaffold.
Bioconjug Chem
; 33(7): 1241-1253, 2022 07 20.
Article
in En
| MEDLINE
| ID: mdl-35801843
Antibody-drug conjugates (ADCs) are a rapidly growing class of cancer therapeutics that seek to overcome the low therapeutic index of conventional cytotoxic agents. However, realizing this goal has been a significant challenge. ADCs comprise several independently modifiable components, including the antibody, payload, linker, and bioconjugation method. Many approaches have been developed to improve the physical properties, potency, and selectivity of ADCs. The anti-HER-2 antibody trastuzumab, first approved in 1998, has emerged as an exceptional targeting agent for ADCs, as well as a broadly used platform for testing new technologies. The extensive work in this area enables the comparison of various linker strategies, payloads, drug-to-antibody ratios (DAR), and mode of attachment. In this review, these conjugates, ranging from the first clinically approved trastuzumab ADC, ado-trastuzumab emtansine (Kadcyla), to the latest variants are described with the goal of providing a broad overview, as well as enabling the comparison of existing and emerging conjugate technologies.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Immunoconjugates
/
Neoplasms
/
Antineoplastic Agents
Type of study:
Systematic_reviews
Limits:
Humans
Language:
En
Journal:
Bioconjug Chem
Journal subject:
BIOQUIMICA
Year:
2022
Document type:
Article
Affiliation country:
Estados Unidos
Country of publication:
Estados Unidos