On June 20, 2023 Adaptam Therapeutics reported the research, co-led by Prof. Asis Palazon, founder and CEO/CSO reveals key insights into the structural dynamics of Siglec-15, an immune system regulator with therapeutic potential (Press release, Adaptam Therapeutics, JUN 20, 2023, View Source [SID1234657089]). The findings offer a detailed understanding of how this target interacts with immune cells, unlocking the possibility for more effective treatments.
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The study, titled "Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b" identifies key mechanisms governing the interaction between Siglec-15 and the immune system. Published in the journal Nature Communications, the study was a collaborative effort led Dr. June Ereño Orbea, Prof. Jesús Jiménez Barbero and Prof. Asis Palazon from CIC bioGUNE. This research contributes to the understanding of novel biology required for the development of innovative drug candidates for cancer immunotherapy.
Prof. Palazon commented: "Our research marks a significant advancement in the field of immunotherapy. By unveiling the precise structure and mechanisms of Siglec-15, we have opened new doors to develop highly targeted therapies, such as monoclonal antibody-based approaches, that could significantly improve outcomes for patients with various cancers."
Recently, Siglec-15 has gained significant interest as a potential therapeutic target due to its distinct expression profile and its potential in cancer treatment. However, the limited understanding of its structure and how it interacts with other molecules had hindered drug development until now.
The study utilized state-of-the-art techniques such as X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and molecular dynamics simulations to achieve these findings. These insights into glycosylation patterns and molecular interactions offer a comprehensive understanding of how Siglec-15 functions within the immune system, specifically its interactions with T cells. The study revealed that the binding of Siglec-15 to STn-lacking T cells depends on the presence of other sialylated glycans. Furthermore, the study identified the leukocyte integrin CD11b as a ligand of Siglec-15 in human T cells. These findings provide a comprehensive understanding of the structural characteristics of Siglec-15 and emphasize the crucial role of glycosylation in controlling the responses of T cells in our immune system.
This research positions Adaptam Therapeutics at the forefront of immunotherapy innovation, contributing to the company’s ongoing drug discovery efforts. "We are excited to translate this knowledge into tangible treatments that target cancer more effectively and with fewer side effects", Prof. Palazon continued.
Publication reference
Lenza MP, Egia-Mendikute L, Antoñana-Vildosola A, et al. Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b. Nat Commun. 2023;14(1):3496. Published 2023 Jun 13.