Summary of preclinical and clinical research progress of anti-tumor antibodies targeting CD47

The CD47 antibody out-license deal reached by Tianjing Bio and Abbvie this week, which reached nearly 2 billion US dollars, once again proved the superstar status of CD47 antibody. Recently, this article titled “Preclinical and Clinical Development of Therapeutic Antibodies Targeting Functions of CD47 in the Tumor Microenvironment” was published by Antibody Therapeutics, a journal of the Chinese Antibody Association and published by Oxford University Press. [1] At that time, the corresponding author of the article was Professor David D. Roberts, a senior researcher at the National Cancer Institute, and the first author was Sukhbir Kaur. The full text in English can be obtained for free via the following link or by clicking “Read the original text” at the bottom left corner of the article:

https://academic.oup.com/abt/article/3/3/179/5889920

Summary and highlights

The purpose of this review is to analyze the data of preclinical studies and clinical trials of monoclonal antibodies, humanized antibodies and bispecific antibodies targeting CD47 through the analysis of the structural and functional characteristics of immune checkpoint CD47, and comprehensively analyze anti-CD47 Challenges and opportunities for therapies in future clinical applications.

Main content

Tumor cells bind to signal-regulated protein α (SIRPα) through high expression of CD47 to transmit anti-phagocytic signals, thereby evading the elimination of the innate immune system represented by macrophages [2]. In recent years, for this anti-phagocytic signaling pathway, more and more antibodies and antagonists have been developed and applied in anti-tumor research (Table 1). This review describes the author’s unique insights into the molecular structure, mechanism of action, development and clinical application of anti-CD47 antibodies in clinical development. At the same time, according to the characteristics of these anti-CD47-SIRPα drug candidates (Table 2) in pre-clinical trials and clinical research and development, the author divided them into CD47 antibodies (B6H12, Vx1000R, BRIC126, mAb400, MIAP301, MAB4670, A4), Humanized CD47 antibody (Hu5F9, SHR-1603, CC-90002, AMMS4-G4, HuNb1, SRF231), SIRPα antibody and fusion protein, CD47 bispecific antibody (CD3xCD47, CD20xCD47, CD47xPD-L1, CD47xEGFR, CD47xMesothelin, CD47xCD19) and several other types. The author pointed out that compared with monoclonal antibodies, bispecific antibodies have better activity, enhance tumor specificity and targeting, and can achieve better therapeutic expectations. These different strategies can provide more candidates for the clinical application of targeted CD47 therapy.

Table 1. Targeting CD47 antibodies and antagonists

The article further pointed out that the widespread expression of CD47 on the surface of blood cells and vascular endothelial cells makes anti-CD47 antibodies cause common transient anemia, hyperbilirubinemia, thrombocytopenia and other side effects. These side effects are the development and application of anti-CD47 antibodies. A big challenge. In order to cope with and solve this problem, Professor Roberts summarized the following coping strategies: 1. Looking for CD47 tumor-specific epitopes. 2. Preparation of bispecific antibodies. 3. For the post-transcriptional modification of CD47, look for new targets that weaken the function of CD47.

Table 2. Ongoing and completed clinical trial projects targeting CD47

Finally, the author made a prospect for the application of anti-CD47 therapy. Although anti-CD47/SIRPα antibodies showed good anti-tumor effects, it was found in some tumor models with normal immunity that the efficacy of these antibodies depends on other combination therapies. , Such as radiotherapy, chemotherapy, immune checkpoint inhibitors targeting PD-1/PD-L1. As a ligand of CD47, TSP-1 also plays an important role in tumor therapy, and the CD47/TSP-1 signal axis also provides a new idea for the development of anti-CD47 therapies.

References

1. Sukhbir Kaur, Kyle V Cicalese, Rajdeep Bannerjee, David D Roberts, Preclinical and clinical development of therapeutic antibodies targeting functions of CD47 in the tumor microenvironment. Antibody Therapeutics 2020, tbaa017.

2. Zhang X, Fan J, Ju D. Insights into CD47/SIRPα axis-targeting tumor immunotherapy. Antibody Therapeutics 2018, 1, 27-32.