The promise and challenges of combination therapies with antibody-drug conjugates in solid tumors

Qing Wei; Peijing Li; Teng Yang; Jiayu Zhu; Lu Sun; Ziwen Zhang; Lu Wang; Xuefei Tian; Jiahui Chen; Can Hu; Junli Xue; Letao Ma; Takaya Shimura; Jianmin Fang; Jieer Ying; Peng Guo; Xiangdong Cheng

doi:10.1186/s13045-023-01509-2

The promise and challenges of combination therapies with antibody-drug conjugates in solid tumors

J Hematol Oncol. 2024 Jan 4;17(1):1. doi: 10.1186/s13045-023-01509-2.

Authors

Qing Wei^#^{1

2

3}, Peijing Li^#^{2

4}, Teng Yang^{2

5}, Jiayu Zhu⁶, Lu Sun^{2

7}, Ziwen Zhang^{1

2}, Lu Wang⁸, Xuefei Tian^{2

9

10}, Jiahui Chen^{2

3

11}, Can Hu^{2

3

11}, Junli Xue¹², Letao Ma^{2

5}, Takaya Shimura¹³, Jianmin Fang¹⁴, Jieer Ying^#^{15

16

17}, Peng Guo^#^{18

19}, Xiangdong Cheng^#^{20

21

22}

Affiliations

¹ Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
² Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.
³ Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, China.
⁴ Department of Radiation Oncology, Zhejiang Cancer Hospital, Key Laboratory of Head and Neck Cancer Translational Research of Zhejiang Province, Hangzhou, China.
⁵ College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China.
⁶ Zhejiang Chinese Medical University, Hangzhou, China.
⁷ Department of Gynecologic Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
⁸ Department of Radiation Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
⁹ Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Shanghai, China.
¹⁰ College of Molecular Medicine, Hangzhou Institute for Advanced Study (HIAS), University of Chinese Academy of Sciences, Hangzhou, China.
¹¹ Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou, China.
¹² Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
¹³ Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
¹⁴ School of Life Science and Technology, Tongji University, Shanghai, China.
¹⁵ Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China. jieerying@aliyun.com.
¹⁶ Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China. jieerying@aliyun.com.
¹⁷ Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, China. jieerying@aliyun.com.
¹⁸ Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China. guopeng@ucas.ac.cn.
¹⁹ Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, China. guopeng@ucas.ac.cn.
²⁰ Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China. chengxd@zjcc.org.cn.
²¹ Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, China. chengxd@zjcc.org.cn.
²² Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou, China. chengxd@zjcc.org.cn.

^# Contributed equally.

Abstract

Antibody-drug conjugates (ADCs) represent an important class of cancer therapies that have revolutionized the treatment paradigm of solid tumors. To date, many ongoing studies of ADC combinations with a variety of anticancer drugs, encompassing chemotherapy, molecularly targeted agents, and immunotherapy, are being rigorously conducted in both preclinical studies and clinical trial settings. Nevertheless, combination therapy does not always guarantee a synergistic or additive effect and may entail overlapping toxicity risks. Therefore, understanding the current status and underlying mechanisms of ADC combination therapy is urgently required. This comprehensive review analyzes existing evidence concerning the additive or synergistic effect of ADCs with other classes of oncology medicines. Here, we discuss the biological mechanisms of different ADC combination therapy strategies, provide prominent examples, and assess their benefits and challenges. Finally, we discuss future opportunities for ADC combination therapy in clinical practice.

Keywords: Antibody-drug conjugate; Combination therapy; Immunotherapy; Solid tumor; Targeted therapy.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents* / therapeutic use
Humans
Immunoconjugates* / therapeutic use
Immunotherapy
Neoplasms* / drug therapy

Substances

Immunoconjugates
Antineoplastic Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding