Pilot Study of Autologous Chimeric Switch Receptor Modified T Cells in Recurrent Glioblastoma Multiforme
Status:
Unknown status
Trial end date:
2019-07-01
Target enrollment:
Participant gender:
Summary
CAR T cell immunotherapy has achieved great success in CD19+ B-cell malignancies. Whether
this new generation of cell-based immunotherapy can be applied to solid tumors remain to be
investigated, partly due to hostile immune-suppressive tumor microenvironment which favors
tumor growth but not immune system. Signaling pathway of programmed death 1 (PD-1) and its
ligand PD-L1 plays an important role in suppressing immune response against tumors. PD-L1 is
over-expressed in 88% of glioblastoma.
We constructed a chimeric switch receptor (CSR) containing the extracellular domain of PD1
fused to the transmembrane and cytoplasmic domain of the costimulatory molecule CD28. CSR
modified T cells are able to recognize PD-L1-expressing tumor cells and transduce signals to
activate T cells, which results in tumor killing. A truncated EGFR (tEGFR) which lacks of the
ligand binding domain and cytoplasmic kinase domain of wildtype EGFR is incorporated into the
CSR vector and is used for in vivo tracking and ablation of CSR T cells when necessary. This
pilot study is to determine the safety and efficacy of autologous CSR T cells in patients
with recurrent glioblastoma.