clec-161 Antibody

CLEC2D/CD161 Axis and Therapeutic Antibodies

The CLEC2D/CD161 pathway is a critical immune checkpoint in cancer immunotherapy. CLEC2D (also known as LLT1 or OCIL) binds to CD161 (KLRB1), a C-type lectin-like receptor expressed on NK cells and subsets of T cells . Antibodies targeting this axis aim to reverse immune suppression in tumors:

IMT-009, a monoclonal antibody against CD161, demonstrates:

• High-affinity binding (IC₅₀ = 0.94 nM) to block CLEC2D-CD161 interactions .

• Restoration of NK and T cell functions:

  • Enhanced NK cytotoxicity (EC₅₀ = 0.2 nM) .

  • Improved T cell receptor signaling (EC₅₀ = 3.5 nM) and cytokine production (TNF-α, IL-2, IFN-γ) .

• Efficacy in solid tumors with high CLEC2D+ and CD161+ cell density, including NSCLC, HNSCC, and TNBC .

CLEC-1 as a Myeloid Checkpoint Target

CLEC-1 is a myeloid cell-specific checkpoint that inhibits phagocytosis of tumor cells. Antibody antagonists against CLEC-1 (e.g., OSE Immunotherapeutics’ candidates) show:

• Synergy with chemotherapy by restoring macrophage phagocytosis .

• Enhanced antigen presentation by dendritic cells .

• Preclinical validation in tumor models, including synergy with anti-SIRPα antibodies .

CLEC-2 (CLEC1B) in Thrombosis and Inflammation

CLEC-2 antibodies like AYP1 and HEL1 modulate platelet activation and thrombosis:

• AYP1: Depletes CLEC-2 for ≥11 days, reducing arterial thrombosis .

• HEL1: Sustained CLEC-2 depletion (≥24 days) with similar antithrombotic effects .

• CLEC-2 blockade also improves liver recovery in acute injury models by enhancing TNF-α-driven neutrophil recruitment .

Antibody Reagents for CLEC Family Members

Commercial antibodies targeting CLEC receptors include:

• Anti-CLEC2 (CLEC1B): BD Biosciences’ BUV615-conjugated antibody (Clone 219133) for flow cytometry .

• Anti-CLEC2D (OCIL): R&D Systems’ PE-conjugated antibody (Clone 402659) validated in lymphoma and autoimmune studies .

• Anti-CLEC-2A: Enhances T cell proliferation via CD161 interaction .

Key Research Gaps and Opportunities

• No direct studies on "clec-161 Antibody" exist in the provided sources.

• Prioritize validation of cross-reactivity between CLEC2D/CD161 antibodies (e.g., IMT-009) and related CLEC family members.

• Explore combination therapies targeting CLEC-1 (myeloid) and CLEC2D (lymphoid) pathways for synergistic effects .