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Development of Effective Siglec-9 Antibodies Against Cancer
Jun Hui Shawn Wang1, Nan Jiang2, Amit Jain2
1Singapore Immunology Network, A*STAR, 8a Biomedical Grove, Singapore, 138648, Singapore.
Purpose Of Review:
This study aims to review state-of-the-art advances in Siglec-9-directed antibodies and to highlight specific aspects of Siglec-9 antibodies that are suitable to mount anti-tumor immunity.
Recent Findings:
Controversies surrounding studies on Siglec-9 antibodies can confound future studies. In this review, we have highlighted some controversies, explained the distinction between Siglec-9 agonistic and antagonistic (endocytic) antibodies, and discussed their suitability in sustaining anti-tumor immunity. Siglec-9 is an immune checkpoint target and an immunoinhibitory receptor that can engage either sialic acid ligands or agonistic antibodies. Through Siglec-9 sialic acid interactions, activated immunoreceptor tyrosine-based inhibitory signaling of the immune cells can lead to unfavorable immunosuppression. To overcome tumor-related immunosuppression, different types of Siglec-9 antibody blockade need to be developed. However, whether a Siglec-9-directed antibody is agonistic or antagonistic is probably affinity-dependent and not epitope-dependent. Additionally, unlike immune-modulatory antibodies such as agonistic antibodies (OX40, CD28, ICOS, and 4-1BB) or Fc-inert antibodies (PD1 and PD-L1) directed against cancer cells, the nature of antagonistic Siglec-9 antibodies is more suitable to enhance anti-tumor immunity and will be discussed.
Insights
This review explores Siglec-9 antibodies for anti-tumor immunity. Antagonistic Siglec-9 antibodies show promise in enhancing anti-tumor responses, unlike agonistic types.
Area of Science:
- Immunology
- Oncology
- Antibody Engineering
Background:
- Siglec-9 is an immunoinhibitory receptor and an immune checkpoint target.
- Siglec-9 interactions with sialic acid ligands can suppress immune cell signaling, contributing to tumor-related immunosuppression.
Purpose of the Study:
- To review advances in Siglec-9-directed antibodies.
- To highlight Siglec-9 antibody aspects suitable for mounting anti-tumor immunity.
- To clarify controversies and distinctions between agonistic and antagonistic Siglec-9 antibodies.
Main Methods:
- Literature review of state-of-the-art advances in Siglec-9 antibodies.
- Analysis of Siglec-9 antibody mechanisms (agonistic vs. antagonistic).
- Discussion of antibody affinity and epitope dependence.
Main Results:
- Siglec-9 antibodies can be agonistic or antagonistic, with this potentially being affinity-dependent.
- Antagonistic Siglec-9 antibodies are more suitable for enhancing anti-tumor immunity compared to agonistic antibodies.
- Distinguishing between antibody types is crucial for developing effective cancer immunotherapies.
Conclusions:
- Antagonistic Siglec-9 antibodies offer a promising strategy to overcome tumor-induced immunosuppression.
- Further research into Siglec-9 antibody blockade is needed to develop effective anti-cancer treatments.
- Understanding Siglec-9 antibody characteristics is key for optimizing cancer immunotherapy.
