Combination of antibody–drug conjugates with immunotherapy: a new paradigm in cancer treatment
- 1The First Clinical Medical College, Shandong University of Traditional Chinese Medicine
- 2School of Traditional Chinese Medicine, Shandong Second Medical University
- 3Department of Oncology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine
Abstract
Immunotherapy, which activates the host immune system to recognize and eliminate tumor cells, has become an important modality in cancer treatments. However, tumor heterogeneity and the immunosuppressive tumor microenvironment often drive resistance to single-agent immunotherapy, thereby limiting its clinical efficacy. Antibody–drug conjugates (ADCs) are a class of targeted anticancer agents composed of a monoclonal antibody, a linker, and a cytotoxic payload. In addition to direct tumor cell killing, ADCs can remodel the tumor microenvironment through multiple mechanisms, thereby contributing to the reversal of immune resistance. Consequently, combination strategies integrating ADCs with immunotherapy have attracted increasing attention. Clinical studies have demonstrated encouraging benefits of ADC–immune checkpoint inhibitor combinations across multiple tumor types, and several emerging regimens have shown promising therapeutic potential. Nevertheless, significant challenges remain in clinical translation. This review summarizes the synergistic mechanisms and recent advances in ADC–immunotherapy combinations, discusses current limitations, and outlines future directions, with the aim of guiding the precise and standardized development of these combination strategies.
Related
- A New Era of Treatment Sequencing in Platinum-Resistant Ovarian Cancer: Integrating Immunotherapy, Antibody-Drug Conjugates, and Targeted Therapies.
- Recent advances in function-enhanced antibody-drug conjugates: Antibody optimization and payload combination
- Epitope selection for combination therapy using antibody-drug conjugates and immune immune-stimulating antibody conjugates
- Antibody‒cell conjugates: A novel "off-the-shelf" modality bridging ADCs and CAR-T for cancer immunotherapy.
- Treatment Sequencing in ARPI-Pre-Exposed Metastatic Castration-Resistant Prostate Cancer: Radioligand Therapy, PARP Inhibitors, and Antibody-Drug Conjugates.
BibTeX
@article{lai2026combination,
title = {{Combination of antibody–drug conjugates with immunotherapy: a new paradigm in cancer treatment}},
author = {Yongli Lai and Ruyu Qin and Zhaidong Liu},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1945452},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1945452/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Combination of antibody–drug conjugates with immunotherapy: a new paradigm in cancer treatment
AU - Yongli Lai
AU - Ruyu Qin
AU - Zhaidong Liu
PY - 2026
DA - 2026/10/22
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1945452
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1945452/full
AB - Immunotherapy, which activates the host immune system to recognize and eliminate tumor cells, has become an important modality in cancer treatments. However, tumor heterogeneity and the immunosuppressive tumor microenvironment often drive resistance to single-agent immunotherapy, thereby limiting its clinical efficacy. Antibody–drug conjugates (ADCs) are a class of targeted anticancer agents composed of a monoclonal antibody, a linker, and a cytotoxic payload. In addition to direct tumor cell killing, ADCs can remodel the tumor microenvironment through multiple mechanisms, thereby contributing to the reversal of immune resistance. Consequently, combination strategies integrating ADCs with immunotherapy have attracted increasing attention. Clinical studies have demonstrated encouraging benefits of ADC–immune checkpoint inhibitor combinations across multiple tumor types, and several emerging regimens have shown promising therapeutic potential. Nevertheless, significant challenges remain in clinical translation. This review summarizes the synergistic mechanisms and recent advances in ADC–immunotherapy combinations, discusses current limitations, and outlines future directions, with the aim of guiding the precise and standardized development of these combination strategies.
SN - 2234-943X
ER -