Singapore Immunology Network, A*STAR, 8a Biomedical Grove, Singapore, 138648, Singapore.
Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 169610, Singapore.
Curr Oncol Rep. 2023 Jan;25(1):41-49. doi: 10.1007/s11912-022-01347-4. Epub 2022 Nov 29.
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.
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.
本研究旨在综述 Siglec-9 导向抗体的最新进展，并强调 Siglec-9 抗体在引发抗肿瘤免疫方面的一些特定特性。
围绕 Siglec-9 抗体的研究存在争议，这可能会使未来的研究复杂化。在这篇综述中，我们强调了一些争议，解释了 Siglec-9 激动型和拮抗性（内吞）抗体之间的区别，并讨论了它们在维持抗肿瘤免疫方面的适用性。Siglec-9 是一种免疫检查点靶点和免疫抑制受体，既能与唾液酸配体结合，也能与激动型抗体结合。通过 Siglec-9 与唾液酸的相互作用，激活的免疫细胞中的免疫受体酪氨酸抑制信号转导可能导致不利的免疫抑制。为了克服与肿瘤相关的免疫抑制，需要开发不同类型的 Siglec-9 抗体阻断剂。然而，Siglec-9 导向抗体是激动型还是拮抗性可能依赖于亲和力，而不是表位依赖性。此外，与针对癌细胞的免疫调节抗体（如激动型抗体（OX40、CD28、ICOS 和 4-1BB）或 Fc 惰性抗体（PD1 和 PD-L1））不同，拮抗性 Siglec-9 抗体的性质更适合增强抗肿瘤免疫，这将在讨论中进行阐述。
