Invariant TCR / NKG2D ligands (tumor cell recognition), no single

Class

Allogeneic, off-the-shelf invariant natural killer T-cell (iNKT) therapy — agenT-797; unmodified iNKT cells expressing an invariant αβ T-cell receptor and NKG2D activating receptor, recognizing stressed/malignant cells and modulating the tumor immune microenvironment

Notes

original target text: Invariant TCR / NKG2D ligands (tumor cell recognition), no single defined myeloma antigen

Invariant natural killer T (iNKT) cells are a rare immune cell type that combines features of T cells and natural killer (NK) cells. Unlike conventional T cells, which recognize a huge variety of peptide fragments displayed by highly variable molecules called MHC, iNKT cells carry a single, fixed T-cell receptor that recognizes lipid molecules presented by CD1d, a molecule that is essentially the same in every person. Because CD1d does not differ between individuals, iNKT cells can potentially be transferred from a donor to a patient without the immune matching normally required for cell therapies, supporting an off-the-shelf, allogeneic approach. iNKT cells also express NKG2D, a second activating receptor that senses stress-associated proteins appearing on the surface of damaged or transformed cells, independent of any particular tumor antigen. This combination allows recognition of malignant cells even in cancers, such as multiple myeloma, that lack one dominant, druggable tumor marker. Upon activation, iNKT cells kill target cells directly and release signaling molecules that recruit and activate other immune cells, reshaping the surrounding tumor environment. This mechanism is relevant across blood cancers and solid tumors where broad, antigen-independent immune surveillance may offer an alternative or complement to therapies that depend on a single defined target.