1332 Anti-CD161 antibody IMT-009 is a novel immunotherapeutic agent that reinvigorates T and NK cell function and anti-tumor efficacy through blocking interaction of CD161 with its ligand CLEC2D

• DOI: 10.1136/jitc-2022-sitc2022.1332
• Publication Date: 2022-11-08T01:25:11Z
• Authors: Alexandria Fusco; Elizabeth Scanlon; Frano Irvine; Flavian Brown; Jeffrey Colbert; Andy Tu; Stephanie Gaerlan; Kelly Nichols; Teresse de Rham; Matthew Huggins; Kendall Dionne; Ming Tang; Heather Flick; Alison Tisdale; Seng-Lai Tan; Shruti Malu
• Keywords: Jurkat cells

<h3>Background</h3> The CLEC2D/CD161 axis is a novel ligand-receptor pathway for immunotherapeutic intervention. IMT-009 monoclonal, aglycosylated human IgG1 antibody directed against CD161, C-type lectin-like receptor, which broadly expressed on NK cells and subsets of both CD4+ CD8+ T [Mathewson et al. 2021]. Its cognate ligand, CLEC2D (LLT1), the surface malignant immune cells, including activated B myeloid cells. <h3>Methods</h3> Functional inhibition CD161 by was demonstrated using several in vitro pharmacological cellular assays assessed cell degranulation, cytokine production cytotoxicity towards tumor targets, as well receptor signaling polyfunctionality primary antigen-specific To prioritize indications that will likely benefit from blockade therapy, multiplexed immunofluorescence analysis over 30 solid types performed. <h3>Results</h3> binds with high affinity selectivity, blocking its interaction at an IC50 0.94 nM. In presence CLEC2D-expressing target K562, targets highly suppressed; can overcome this EC50 0.2 Similarly, reversed CLEC2D-mediated restored Jurkat reporter system (EC50 = 3.5 nM), enhanced secretion TNF-α, IL2, IFNγ nM, 0.4 1.4 respectively), direct mediated cytotoxicity. also released CD161-mediated suppression effector memory CD161+ resulting increased frequency IFN-γ+ increase their proliferation indicative stronger recall response to antigen. Finally, data showed highest density CLEC2D+ following indications: NSCLC-squamous carcinoma, NSCLC- adenocarcinoma, Head Neck squamous carcinoma (HNSCC), Triple negative breast cancer (TNBC), Cutaneous Colorectal carcinoma. <h3>Conclusions</h3> These results support development immunotherapy application indications. <h3>References</h3> Mathewson N, Ashenberg O, Tirosh I, Inhibitory identified glioma-infiltrating single-cell analysis.<i> Cell.</i> 2021;184:1281–1298. Iliopoulou IG, Karamouzis M-V, Missitzis Increased Frequency Cells Expressing Cancer Patients. <i>Clin Res</i> 2006;12:6901-6909.