Allakos Presents Preclinical Data on AK007, a Siglec-10 Antagonist Antibody, at the Society for Immunotherapy of Cancer’s 37th Annual Meeting
– Siglec-10 is a myeloid checkpoint receptor selectively expressed on tumor associated macrophages and dendritic cells –
– AK007 potently blocks all known ligand interaction with Siglec-10, including the “don’t eat me” signal CD24 –
– Monotherapy treatment with a Siglec-10 antagonist antibody polarized tumor-associated myeloid cells and reduced tumor burden in pre-clinical studies –
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
- 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 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.
Forward Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 as contained in Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Such forward-looking statements include, but are not limited to, Allakos’ progress, business plans and areas of focus, the potential of AK007, and the initiation of a first-in-human study with AK006. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from current expectations and beliefs, including but not limited to: Allakos’ stages of clinical drug development; Allakos’ ability to timely initiate and complete pre-clinical trials for AK007; Allakos’ ability to timely initiate and complete clinical trials for lirentelimab and AK006; Allakos’ ability to obtain required regulatory approvals for its clinical trials; uncertainties related to the enrollment of patients in its clinical trials; Allakos’ ability to demonstrate sufficient safety and efficacy of its product candidates in its clinical trials; uncertainties related to the success of clinical trials, regardless of the outcomes of pre-clinical testing or early-stage trials; Allakos’ ability to obtain regulatory approvals to market its product candidates; market acceptance of Allakos’ product candidates; uncertainties related to the projections of the size of patient populations suffering from the diseases
Source: Allakos Inc.