Definition

A preparation of autologous T lymphocytes that have been genetically engineered to express a T-cell receptor (TCR) specific for the histone H3.3 containing the amino acid substitution mutation lysine (Lys) 27-to-methionine (H3.3K27M), with potential immunomodulating and antineoplastic activities. Upon administration, the autologous anti-H3.3K27M TCR-expressing T cells specifically target and bind to H3.3K27M-expressing tumor cells. This leads to T-cell activation and T-cell mediated lysis of H3.3K27M-expressing tumor cells. The H3.3K27M mutation alters the methylation and acetylation profile of the histone H3 variant H3.3 at Lys 27. Modification of H3.3 at Lys 27 regulates gene expression, and the H3.3K27M mutation occurs in a variety of cancer cell types.