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Progress of CD47 immune checkpoint blockade agents in anticancer therapy: a hematotoxic perspective

  • Review – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

CD47, a transmembrane protein, acts as a “do not eat me” signal that is overexpressed in many tumor cell types, thereby forming a signaling axis with its ligand signal regulatory protein alpha (SIRPα) and enabling the tumor cells to escape from macrophage-mediated phagocytosis. Several clinical trials with CD47 targeting agents are underway and have achieved impressive results preliminarily. However, hematotoxicity (particularly anemia) has emerged as the most common side effect that cannot be neglected. In the development of CD47 targeting agents, various methods have been used to mitigate this toxicity. In this review, we summarized five strategies used to alleviate CD47 blockade-induced hematotoxicity, as follows: change in the mode of administration; dual targeting bispecific antibodies of CD47; CD47 antibodies/SIRPα fusion proteins with negligible red blood cell binding; anti-SIRPα antibodies; and glutaminyl-peptide cyclotransferase like inhibitors. With these strategies, the development of CD47 targeting agents can be improved.

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Abbreviations

ADCC:

Antibody-dependent cell-mediated cytotoxicity

ADCP:

Antibody-dependent cellular phagocytosis

CD19:

Cluster of differentiation 19

CD20:

Cluster of differentiation 20

CD47:

Cluster of differentiation 47

CTLA-4:

Cytotoxic T lymphocyte-associated molecule-4

DLBCL:

Diffuse large B-cell lymphoma

EGFR:

Epidermal growth factor receptor

HER2:

Human epidermal growth factor receptor-2

MTD:

Maximum tolerated dose

PD-1:

Programmed cell death receptor-1

PD-L1:

Programmed cell death ligand-1

QPCT:

Glutaminyl-peptide cyclotransferase

QPCTL:

Glutaminyl-peptide cyclotransferase like

RBC:

Red blood cell

SIRPα:

Signal regulatory protein alpha

SIRPβ:

Signal regulatory protein beta

SIRPγ:

Signal regulatory protein gamma

TAA:

Tumor-associated antigens

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Acknowledgements

We express great thanks to Dr. Le-Le Zhang for the language polishing to our manuscript.

Funding

This work was funded by The Science and Technology Development Fund, Macau SAR (File no. 0129/2019/A3) and was partially supported by National Natural Science Foundation of China (81973516).

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Author notes

  1. Yu-Chi Chen and Wei Shi contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China

    Yu-Chi Chen, Wei Shi, Jia-Jie Shi & Jin-Jian Lu

  2. Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Macao, China

    Jin-Jian Lu

  3. MoE Frontiers Science Center for Precision Oncology, University of Macau, Macao, China

    Jin-Jian Lu

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  1. Yu-Chi Chen
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  2. Wei Shi
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Y-CC and WS wrote the main manuscript text. Y-CC drew the figures. J-JS, Y-CC and WS collected and analyzed the data. J-JL and J-JS provided suggestions and revisions. All the authors read and approved the final manuscript.

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Correspondence to Jia-Jie Shi or Jin-Jian Lu.

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Chen, YC., Shi, W., Shi, JJ. et al. Progress of CD47 immune checkpoint blockade agents in anticancer therapy: a hematotoxic perspective. J Cancer Res Clin Oncol 148, 1–14 (2022). https://doi.org/10.1007/s00432-021-03815-z

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