CD161 (KLRB1)

Class

Fc-attenuated IgG1 monoclonal antibody (immune checkpoint blocker)

Pathway

CD161-CLEC2D axis blockade restoring T and NK cell anti-tumor activity

CD161, encoded by the gene KLRB1, is an inhibitory receptor found on subsets of T cells and natural killer (NK) cells. It binds a partner molecule called CLEC2D (also known as LLT1), which is expressed on various tissues and can be upregulated by tumors. When CD161 engages CLEC2D, it dampens the killing activity of the T or NK cell, providing a natural brake on immune responses. Tumors can exploit this axis to blunt anti-tumor immunity, similar in concept to other checkpoint pathways such as PD-1/PD-L1. Blocking the CD161-CLEC2D interaction with an antibody is intended to release this brake, restoring the cytotoxic capacity of T and NK cells against malignant cells. This mechanism is of interest in cancers where CD161-expressing lymphocyte populations are present within the tumor microenvironment and where CLEC2D is upregulated. Because the antibody in this class carries an Fc-attenuated backbone, it is designed to block the inhibitory signal without triggering depletion of the very immune cells it is meant to reinvigorate. This approach broadly fits within the field of immune checkpoint blockade, which seeks to counteract tumor-driven immune suppression across multiple cancer types.