Targeting collagen in tumor extracellular matrix as a novel targeted strategy in cancer immunotherapy

Jiayang Liu; Danjie Pan; Xuan Huang; Songna Wang; Huaning Chen; Yi Zhun Zhu; Li Ye

doi:10.3389/fonc.2023.1225483

Targeting collagen in tumor extracellular matrix as a novel targeted strategy in cancer immunotherapy

Front Oncol. 2023 Aug 24:13:1225483. doi: 10.3389/fonc.2023.1225483. eCollection 2023.

Authors

Jiayang Liu^{1

2}, Danjie Pan^{1

2

3}, Xuan Huang^{1

2

3}, Songna Wang^{1

2

3}, Huaning Chen^{1

2

3}, Yi Zhun Zhu³, Li Ye^{1

3}

Affiliations

¹ Department of Biological Medicines at School of Pharmacy, Minhang Hospital, Fudan University, Shanghai, China.
² Shanghai Engineering Research Center of Immunotherapeutics, School of Pharmacy, Fudan University, Shanghai, China.
³ School of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, Macau SAR, China.

Abstract

Collagen, the most abundant protein in mammal, is widely expressed in tissues and organs, as well as tumor extracellular matrix. Tumor collagen mainly accumulates in tumor stroma or beneath tumor blood vessel endothelium, and is exposed due to the fragmentary structure of tumor blood vessels. Through the blood vessels with enhanced permeability and retention (EPR) effect, collagen-binding macromolecules could easily bind to tumor collagen and accumulate within tumor, supporting tumor collagen to be a potential tumor-specific target. Recently, numerous studies have verified that targeting collagen within tumor extracellular matrix (TEM) would enhance the accumulation and retention of immunotherapy drugs at tumor, significantly improving their anti-tumor efficacy, as well as avoiding severe adverse effects. In this review, we would summarize the known collagen-binding domains (CBD) or proteins (CBP), their mechanism and application in tumor-targeting immunotherapy, and look forward to future development.

Keywords: cancer immunotherapy; collagen; collagen-binding domain; collagen-binding protein; tumor targeting.

Publication types

Review

Grants and funding

This study was supported by Macau Science and Technology Development fund (FDCT 0148/2022/A3), Faculty Research Grants of Macau University of Science and Technology (No. FRG-22-090-SP), and Scientific and Innovative Action Plan of Shanghai (No. 20S11901600 and 18431902800).