TY - JOUR

T1 - Antibody–Drug Conjugates

T2 - The Dynamic Evolution from Conventional to Next-Generation Constructs

AU - Metrangolo, Virginia

AU - Engelholm, Lars H.

N1 - Publisher Copyright: © 2024 by the authors.

PY - 2024

Y1 - 2024

N2 - Introduced almost two decades ago, ADCs have marked a breakthrough in the targeted therapy era, providing clinical benefits to many cancer patients. While the inherent complexity of this class of drugs has challenged their development and broad application, the experience gained from years of trials and errors and recent advances in construct design and delivery have led to an increased number of ADCs approved or in late clinical development in only five years. Target and payload diversification, along with novel conjugation and linker technologies, are at the forefront of next-generation ADC development, renewing hopes to broaden the scope of these targeted drugs to difficult-to-treat cancers and beyond. This review highlights recent trends in the ADC field, focusing on construct design and mechanism of action and their implications on ADCs’ therapeutic profile. The evolution from conventional to innovative ADC formats will be illustrated, along with some of the current hurdles, including toxicity and drug resistance. Future directions to improve the design of next-generation ADCs will also be presented.

AB - Introduced almost two decades ago, ADCs have marked a breakthrough in the targeted therapy era, providing clinical benefits to many cancer patients. While the inherent complexity of this class of drugs has challenged their development and broad application, the experience gained from years of trials and errors and recent advances in construct design and delivery have led to an increased number of ADCs approved or in late clinical development in only five years. Target and payload diversification, along with novel conjugation and linker technologies, are at the forefront of next-generation ADC development, renewing hopes to broaden the scope of these targeted drugs to difficult-to-treat cancers and beyond. This review highlights recent trends in the ADC field, focusing on construct design and mechanism of action and their implications on ADCs’ therapeutic profile. The evolution from conventional to innovative ADC formats will be illustrated, along with some of the current hurdles, including toxicity and drug resistance. Future directions to improve the design of next-generation ADCs will also be presented.

KW - antibodies

KW - antibody–drug conjugates

KW - cancer immunotherapy

KW - engineering

KW - internalization

KW - targeted therapy

U2 - 10.3390/cancers16020447

DO - 10.3390/cancers16020447

M3 - Review

C2 - 38275888

AN - SCOPUS:85183392583

VL - 16

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 2

M1 - 447

ER -