Multi-target combinatory strategy to overcome tumor immune escape

Abstract

Immune therapy has become the fourth approach after surgery, chemotherapy, and radiotherapy in cancer treatment. Many immune checkpoints were identified in the last decade since ipilimumab, which is the first immune checkpoint inhibitor to cytotoxic T-lymphocyte associated protein 4, had been approved by the US Food and Drug Administration (FDA) for the treatment of unresectable or metastatic melanoma in 2011. The use of several antibody drugs that target PD1/PD-L1 for various cancer treatments has been approved by the FDA. However, fewer people are benefitting from immune checkpoint inhibitor treatment in solid cancers. Approximately 80% of patients do not respond appropriately because of primary or acquired therapeutic resistance. Along with the characterization of more immune checkpoints, the combinatory treatment of multi-immune checkpoint inhibitors becomes a new option when monotherapy could not receive a good response. In this work, the author focuses on the combination therapy of multiple immune checkpoints (does not include targeted therapy of oncogenes or chemotherapy), introduces the current progression of multiple immune checkpoints and their related inhibitors, and discusses the advantages of combination therapy, as well as the risk of immune-related adverse events.

Keywords

immune checkpoints / multi-target / immune escape / immune-related adverse events / combination therapy

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Acknowledgements

This project was partially supported by the National Natural Science Foundation of China (Nos. 82072602 and 81772505) to Yingyan Yu, the Shanghai Science and Technology Committee (Nos. 20DZ2201900 and 18411953100) to Yingyan Yu, the Chinese National Key Program (Nos. MOST-2017YFC0908300 and 2016YFC1303200) to Yingyan Yu, and the Innovation Foundation of Translational Medicine of Shanghai Jiao Tong University School of Medicine (No. TM202001) to Yingyan Yu.

Compliance with ethics guidelines

Yingyan Yu declares no conflicts of interest. This article does not involve a research protocol that requires the approval of a relevant institutional review board or ethics committee.

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