NCIt definition : Autologous human CD8-positive T-lymphocytes transduced with a recombinant retroviral
vector encoding a chimeric T cell receptor (chimeric antigen receptor or CAR) consisting
of an anti-vascular endothelial growth factor receptor type 2 (VEGFR2) scFv (single
chain variable fragment), linked to the transmembrane domain of human CD8alpha and
coupled to the costimulatory signaling domains of both CD28 and 4-1BB (CD137), and
the CD3 zeta chain of the T-cell receptor (TCR), with potential immunostimulating
and antineoplastic activities. Autologous peripheral blood lymphocytes (PBLs) from
a patient with VEGFR2-positive cancer are pulsed with a retroviral vector that encodes
the CAR gene specific for VEGFR2. After expansion in culture and reintroduction into
the patient, the anti-VEGFR2 CAR-gene engineered CD8 lymphocytes express anti-VEGFR2-CAR
on their cell surfaces and bind to the VEGFR2 antigen on tumor cell surfaces. Subsequently,
VEGFR2-expressing tumor cells are lysed. VEGFR2, a receptor tyrosine kinase (RTK)
overexpressed by a variety of cancer cell types, belongs to the VEGFR superfamily
and plays key roles in tumor cell proliferation, survival, invasion and tumor angiogenesis.
The co-stimulatory molecules are required for optimal T-cell activation.;