Method of treating glioblastoma multiforme

A method of treating glioblastoma multiforme (GBM) in a subject, the method comprising:

• a) resecting a glioblastoma multiforme (GBM) tumor from the subject, wherein the resecting creates a cavity formerly occupied by tumor tissue;
• b) administering a genetically modified T cell expressing on its cell surface a chimeric T cell antigen receptor comprising a heterologous binding domain that specifically binds to EGFRvIII expressed on the surface of cells of the cancer, and an intracellular signaling domain, wherein binding of the heterologous binding domain to the tumor antigen on the surface of a cancer cell activates the intracellular signaling domain and the T cell, and wherein the genetically modified T cell is encapsulated in a matrix placed in the resection cavity;
• and
• c) administering a first genetically modified mesenchymal stem cell, that expresses an Interleukin-12 (IL-12) polypeptide, wherein the genetically modified mesenchymal stem cell is encapsulated in a matrix placed in the resection cavity,
• wherein the heterologous immunomodulatory polypeptide potentiates GBM cancer cell killing by the genetically modified T cell.