Robust Armored Dual-Cytokine (IL-15/IL-21) GPC3-CAR T Cells for Atypical Teratoid Rhabdoid Tumors and Central Nervous System Rhabdoid Tumors (RADIANT)
Baylor College of Medicine
Summary
This study is being conducted in patients with GPC3-positive brain tumors that have recurred or have not responded to standard therapy. Atypical teratoid rhabdoid tumors (ATRT) are aggressive tumors with poor outcomes and limited treatment options, particularly in young children. There is a need for new therapies that can improve outcomes while minimizing toxicity. This study evaluates a new experimental treatment using genetically engineered T cells (RADIANT-T cells) that target glypican-3 (GPC3), a protein expressed on tumor cells. These T cells are modified to express a chimeric antigen receptor (CAR) targeting GPC3, along with IL-15 and IL-21 to enhance their persistence and activity. The cells also include an inducible safety mechanism (iCasp9) that allows them to be eliminated if necessary. The purpose of this study is to determine the highest safe dose of RADIANT-T cells, evaluate their safety and side effects, assess how long they persist in the body, and determine whether they show anti-tumor activity in patients with GPC3-positive brain tumors.
Description
This is a Phase 1 dose-escalation study conducted at Texas Children's Hospital to evaluate RADIANT-T cells in patients with GPC3-positive brain tumors. Approximately 15-24 subjects will participate in the treatment portion of the study. Autologous T cells are collected from the patient and genetically engineered using a retroviral vector to express a GPC3-specific chimeric antigen receptor along with IL-15 and IL-21. The modified T cells are expanded and tested for activity against GPC3-positive tumor cells prior to administration. Patients receive a single dose of RADIANT-T cells administer…
Eligibility
- Age range
- 1–21 years
- Sex
- All
- Healthy volunteers
- No
Procurement Inclusion Criteria: * 1\) Diagnosis of GPC3-positive recurrent ATRT. * 2\) Age ≥ 6 months * 3\) Karnofsky/Lansky score ≥ 60% * 4\) Informed consent explained to, understood by, and signed by patient/guardian; copy provided * 5\) GPC3 expression by immunohistochemistry with extent score ≥ Grade 2 (\>25% positive tumor cells) and intensity score ≥ 2 (scale 0-4) Procurement Exclusion Criteria: * 1\) No history of organ transplantation * 2\) No known HIV positivity * 3\) No active bacterial, fungal, or viral infection (except Hepatitis B or Hepatitis C virus infections) * 4\) No oth…
Interventions
- Biological21.15.GPC3-CAR T Cells
Autologous T cells genetically engineered using retroviral vectors encoding a GPC3-specific CAR and IL-15 and IL-21 cytokines. The product also includes an inducible caspase-9 safety switch allowing pharmacologic elimination of the CAR T cells in the event of severe toxicity.
Location
- Texas Children's HospitalHouston, Texas