Clinical Trial Finder

Inclusion Criteria:

1. Participants must have diffuse intrinsic pontine glioma at any timepoint following completion of standard radiotherapy. 2. Age 1-18 years. 3. Sex: Male or female. 4. CNS reservoir catheter, such as an Ommaya or Rickham catheter, present in the proper location for CNS-directed therapy. 5. Performance status: Lansky or Karnofsky score >= 60. 6. Life expectancy >= 8 weeks. 7. Normal organ function: 7.1 AST (SGOT) < 5 times the upper limit of normal (ULN) 7.2 ALT (SGPT) < 5 times the upper limit of normal (ULN) 7.3 Total bilirubin < 3 times the upper limit of normal (ULN) 7.4 Creatinine < 5 times the upper limit of normal (ULN) 7.5 SpO2 room air >=90% 8. Prior therapy wash-out before planned leukapheresis 8.1 >= 7 days post last chemotherapy/biologic therapy administration 8.2 3 half-lives or 30 days, whichever is shorter after the last dose of antitumor antibody therapy 8.3 At least 30 days from most recent cellular infusion 8.4 All systemically administered corticosteroid treatment therapy must be stable or decreasing within 1 week prior to enrollment with a maximum dexamethasone dose of 2.5 mg/m2/day. Corticosteroid physiologic replacement therapy is allowed. 9. Participants and/or legal guardians must have the ability to understand and willingness to sign a written informed consent and/or assent document.

Exclusion Criteria:

1. Presence of >= grade 3 cardiac dysfunction or symptomatic arrythmia requiring intervention. 2. Presence of primary immunodeficiency or bone marrow failure syndrome. 3. Presence of clinical and/or radiographic evidence of impending herniation of CNS. 4. Presence of > Grade 3 dysphagia. 5. History of active malignancy other than nonmelanoma skin cancer and carcinoma in situ (e.g., cervix, bladder, breast). 6. Presence of uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities, or psychiatric illness/social situations that would limit compliance with study requirements. 7. Pregnant or breastfeeding women were excluded from this study because CAR-T-cell therapy may be associated with the potential for teratogenic or abortifacient effects. Women of childbearing potential must have a negative serum pregnancy test. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CAR-T cells, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study. Participants of childbearing or child-fathering potential must be willing to practice birth control from the time of enrollment in this study and for four months after receiving CAR-T-cell infusion. 8. Serologic status reflecting active HIV, hepatitis B or C infection. Participants who are positive for hepatitis B core antibody, hepatitis B surface antigen or hepatitis C antibody must have negative PCR prior to enrollment.

The brain tumor known as Diffuse Intrinsic Pontine Glioma is commonly found in children aged between 5 to 10 years. This type of tumor is aggressive and infiltrates the structures of the brain stem. Treatment options are limited due to the location of the tumor, making it impossible to surgically remove the mass like other brain cancers. The standard treatment for this type of tumor is radiation therapy, as this type of cancer does not respond to chemotherapy or currently available targeted drugs. However, radiation therapy has been found to be ineffective and does not improve survival rates. Currently, there is development in cancer treatment using immunotherapy, where the patient's immune cells are genetically modified to target the cancer, also known as CAR T cells, for the treatment of recurrent or refractory cancers in solid tumors and brain cancers. The research project aims to study the efficacy and safety of treating patients with pontine glioma using T cells that are antigen-specific and have signals from the interleukin-7 receptor alpha and are specific to the B7H3 antigen on the tumor surface. This research is the first of its kind in Thai patients. The research project expects that this treatment will be highly safe and effective in controlling diffuse pontine glioma.

Arms

Experimental: Locoregional delivery of B7H3/IL-7Ra CAR T cell in DIPG

Patients with DIPG for whom CAR T cells will be delivered into the ventricular system Interventions: Biological: Autologous B7H3-specific chimeric antigen receptor (CAR) T cell with additional of IL-7Ra signaling domain Dose level: 1x10e7 CAR T cell, 3x10e7 CAR T cell, 10x10e7 CAR T cell

Interventions

Biological: - B7H3 specific CAR T cell with IL-7Ra signaling domain

Autologous T cells lentivirally transduced to express a B7H3 specific chimeric antigen receptor (CAR) with additional of IL-7 receptor alpha signalingdomain given via indwelling central nervous system (CNS) catheter