On November 10, 2022 Allakos Inc. (Nasdaq: ALLK), a clinical-stage biotechnology company developing therapeutics which target immunomodulatory receptors present on immune effector cells involved in allergy, inflammatory and proliferative diseases, reported a poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 37TH Annual Meeting (Press release, Allakos, NOV 10, 2022, View Source [SID1234623682]). The poster presentation highlights pre-clinical data supporting Siglec-10 as a promising myeloid target for enhancing anti-tumor immunity in solid tumors.
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SITC Poster Details:
The poster titled "Antibody blockade of the immunoinhibitory receptor Siglec-10 polarizes tumor-associated myeloid cells and promotes anti-tumor immunity" will be presented on Friday, November 11TH, key findings include:
Siglec-10 is a myeloid inhibitory checkpoint receptor selectively expressed on tumor associated macrophages (TAMs) and dendritic cells (DCs)
Siglec-10 expression is upregulated in multiple solid cancers and inversely correlates with patient survival in colon adenocarcinoma
Siglec-10 antagonist mAb monotherapy treatment inhibited tumor growth in a syngeneic colon adenocarcinoma model in Siglec-10 transgenic mice
Reduced tumor growth was associated with an expansion and activation of TAMs, dendritic cells, and T lymphocytes in the tumor, consistent with the mechanism of action
The poster is both available on the SITC (Free SITC Whitepaper) website (Abstract ID: 1396) as well as the Allakos Scientific Presentations page.
About Siglec-10 and AK007
In proliferative diseases like cancer, blocking immune inhibitory checkpoint receptors can restore the immune system’s ability to identify and kill tumor cells. Therapeutics that target T cell checkpoint receptors, such as PD-1 and CTLA-4, or their ligands, were the first to demonstrate meaningful anti-tumor activity by blocking immune cell inhibition (i.e. removing the brakes).
More recently, ‘don’t eat me’ signals, such as CD47 and CD24, have been identified to be overexpressed in tumors and allow cancer cells to avoid destruction by macrophages and other myeloid cells of the innate immune system. Restoring myeloid cell function has the potential to increase anti-tumor immunity by activating both innate and adaptive immune cells. Strategies which target ‘don’t eat me’ signals or their myeloid checkpoint receptors represent attractive targets for the treatment of cancer.
Siglec-10 is a checkpoint receptor selectively expressed on tumor associated macrophages (TAMs) and dendritic cells (DCs). Siglec-10 functions as an inhibitory receptor through interaction with multiple ligands, including the ‘don’t eat me’ signal CD24 as well as CD52 and VAP-1. Siglec-10 induces immunosuppression and promotes tumor immune escape through interaction with CD24. Similarly, CD52 has been shown to induce inhibition via Siglec-10, indicating that Siglec-10 functions as an inhibitory receptor through multiple ligands. Siglec-10 is elevated in multiple tumor types and increased expression has been inversely correlated with patient survival in multiple solid tumors, suggesting that Siglec-10 may play a role in tumor evasion.
AK007 is a humanized Siglec-10 antagonist antibody designed to block Siglec-10 interaction with all known ligands (CD24, CD52, and VAP-1). By targeting Siglec-10, AK007 has the potential to reverse myeloid suppression and promote anti-tumor immunity by directly blocking the checkpoint receptor irrespective of individual ligand interaction.
Allakos is currently conducting additional pre-clinical studies with AK007.