Definition

A preparation of autologous T lymphocytes genetically modified to express a chimeric antigen receptor (CAR) comprised of a CD28 co-stimulatory signaling domain fused to the zeta chain of the TCR/CD3 complex (CD3zeta) and coupled to chlorotoxin (CLTX), a 36-amino acid peptide derived from the venom of the deathstalker scorpion, with potential immunomodulating and antineoplastic activities. Upon administration of autologous CLTX-targeted CAR T lymphocytes CHM 1101, the CAR-T cells are re-directed to specific brain tumor cells through its tumor-targeting domain CLTX. CLTX targets and binds to the membrane-bound endopeptidase matrix metalloproteinase-2 (MMP-2), thereby inducing selective toxicity in MMP-2-expressing tumor cells. MMP-2 is specifically upregulated in gliomas and related cancers, but is not normally expressed in the brain.