GPC-3 Chimeric Antigen Receptor T Cells FOR Recurrent GPC-3 Positive Glioblastoma
Baylor College of Medicine
Summary
The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: antibodies and T cells. Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T-cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat participants with cancers. They have shown promise, but have not been strong enough to cure most participants. The study team has found from previous research that we can put a new gene (a tiny part of what makes-up DNA and carries the participants traits) into T cells that will make them recognize cancer cells and kill them. In the lab, the study team has made several genes called a chimeric antigen receptor (CAR), from an antibody called GC33. The antibody GC33 recognizes a protein found on the participants brain tumor. This CAR is called GPC3-CAR. To make this CAR more effective, the study has also added a gene that includes IL15. IL15 is a protein that helps CAR T cells grow better and stay in the blood longer so that they may kill tumors better. The mixture of GPC3-CAR and IL15 killed tumor cells better in the laboratory when compared with CAR T cells that did not have IL15. This study will test T cells with the IL15 GPC3-CAR (GO-CART T cells) in participants with GPC3-positive brain tumors. T cells made to carry a gene called iCasp9 can be killed when they encounter a specific drug called AP1903. The study team will insert the iCasp9 and IL15 together into the T cells using a virus that has been made for this study. The drug (AP1903) is an experimental drug that has been tested in humans with no bad side-effects. The study team will use this drug to kill the T cells if necessary due to side effects. This study will test T cells genetically engineered with a GPC3-CAR and IL15 (GO-CART T cells) in participants with GPC3-positive brain tumors. The GO-CART T cells are an investigational product not approved by the Food and Drug Administration.
Description
The study team will collect up to 180 mL (approximately 12 tablespoons) of participants blood. This will be used to grow T cells. The study team grows the T cells and uses a retrovirus (a special virus that can insert the GPC3 CAR and IL15 genes into the T cells) to genetically engineer them. After the CAR and IL15 genes were put into the T cells, the study team ensures that they could kill GPC3 positive solid tumor cells in the laboratory. WHAT THE TREATMENT WILL BE LIKE: After making these cells, they were frozen. If the participant agrees to participate in this study, at the time they are…
Eligibility
- Age range
- 21–70 years
- Sex
- All
- Healthy volunteers
- No
Procurement Inclusion Criteria: * Diagnosis of GPC3-positive recurrent glioblastoma with previous resection planned for repeat resection. * Age ≥18 years * Karnofsky score ≥60% * Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent * GPC3 expression (as determined by immunohistochemistry) with an extent score of ≥ Grade 2 (\>25% positive tumor cells) and an intensity score of ≥ 2 (scale 0-4). Procurement Exclusion Criteria: * History of hypersensitivity reactions to murine protein-containing products OR presence of huma…
Interventions
- Genetic15.GPC3-CAR T cells
Four different dosing schedules will be evaluated. The following dose levels will be evaluated: DL1: 5x10\^6 DL2: 1x10\^7 DL3: 5x10\^7 DL4: 1x10\^8
Location
- Baylor St. Luke's Medical CenterHouston, Texas