RAD3CAR is a phase I study designed to evaluatethe safety of B7-H3-CAR T cells and lymphodepletion in combination with hypofractionated radiation therapy.
Primary objective:
- To evaluate the safety of B7-H3-CAR T cell therapy after priming with hypofractionated radiation therapy (HFRT) and lymphodepleting chemotherapy in patients ≤ 21 years of age with relapsed/refractory B7-H3+ sarcomas.
Secondary objectives:
* To describe the antitumor activity of B7-H3-CAR T cells in combination with HFRT
* To determine if B7-H3-CAR T cells traffic to tumor sites after combination treatment with HFRT

Start Date21 Jan 2026

Sponsor / Collaborator

St. Jude Children's Research Hospital, Inc.

NCT05835687

/ RecruitingPhase 1IIT

Loc3CAR: Locoregional Delivery of B7-H3-specific Chimeric Antigen Receptor Autologous T Cells for Pediatric Patients With Primary CNS Tumors

Loc3CAR is a Phase I clinical trial evaluating the use of autologous B7-H3-CAR T cells for participants ≤ 21 years old with primary CNS neoplasms. B7-H3-CAR T cells will be locoregionally administered via a CNS reservoir catheter. Study participants will be divided into two cohorts: cohort A with B7-H3-positive relapsed/refractory non-brainstem primary CNS tumors, and cohort B with diffuse midline gliomas (DMG). Participants will receive four (4) B7-H3-CAR T cell infusions over a 4 week period. The purpose of this study is to find the maximum (highest) dose of B7-H3-CAR T cells that are safe to give patients with primary brain tumors.
Primary objectives
* To determine the safety, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for the locoregional delivery of autologous B7-H3-CAR T cells in patients ≤ 21 years of age with recurrent/refractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B).
Secondary objectives
* To assess the efficacy, defined as sustained objective response, a partial response (PR) or complete response (CR) observed anytime on active treatment with B7-H3-CAR T cells in patients with relapsed/refractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B).
* To characterize and monitor neurologic toxicities in patients while on study (Cohort A and B).

Start Date27 Apr 2023

Sponsor / Collaborator

St. Jude Children's Research Hospital, Inc.

NCT04897321

/ RecruitingPhase 1IIT

B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)

3CAR is being done to investigate an immunotherapy for patients with solid tumors. It is a Phase I clinical trial evaluating the use of autologous T cells genetically engineered to express B7-H3-CARs for patients ≤ 21 years old, with relapsed/refractory B7-H3+ solid tumors. This study will evaluate the safety and maximum tolerated dose of B7-H3-CAR T cells.The purpose of this study is to find the maximum (highest) dose of B7-H3-CAR T cells that are safe to give to patients with B7-H3-positive solid tumors.
Primary objective
To determine the safety of one intravenous infusion of autologous, B7-H3-CAR T cells in patients (≤ 21 years) with recurrent/refractory B7-H3+ solid tumors after lymphodepleting chemotherapy
Secondary objective
To evaluate the antitumor activity of B7-H3-CAR T cells
Exploratory objectives
* To evaluate the tumor environment after treatment with B7-H3-CAR T cells
* To assess the immunophenotype, clonal structure and endogenous repertoire of B7-H3-CAR T cells and unmodified T cells
* To characterize the cytokine profile in the peripheral blood after treatment with B7-H3-CAR T cells

Start Date06 Jul 2022

Sponsor / Collaborator

St. Jude Children's Research Hospital, Inc.

100 Clinical Results associated with B7-H3-CAR T cells(St. Jude Children's Research Hospital)

100 Translational Medicine associated with B7-H3-CAR T cells(St. Jude Children's Research Hospital)

100 Patents (Medical) associated with B7-H3-CAR T cells(St. Jude Children's Research Hospital)

Literatures (Medical) associated with B7-H3-CAR T cells(St. Jude Children's Research Hospital)

01 May 2026·NEURO-ONCOLOGY

Preclinical efficacy of combinatorial B7-H3 CAR T cells and ONC206 against diffuse intrinsic pontine glioma

Article

Author: Meechan, Michael ; Wendler, Jason P ; Toumi, Ryma ; Kordowski, Anja ; Oda, Shannon K ; Koschmann, Carl ; Vitanza, Nicholas A ; Pattwell, Siobhan ; Dun, Matthew D ; Song, Edward Z ; Ronsley, Rebecca ; Foster, Jessica B ; Winter, Lily ; Jensen, Michael C ; Timpanaro, Andrea ; Biery, Matthew C ; Gustafson, Joshua A ; Johnson, Scott ; Nemec, Kelsey M ; Rajendran, Ashmitha ; Lau, Davina ; Evans, Myron ; Elena-Sanchez, Leonel ; Piccand, Caroline

Abstract:

Background:

Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric brain tumor affecting over 300 children annually in the United States. Chimeric antigen receptor (CAR) T cells are a targeted immune effector cell therapy with substantial clinical benefit against hematologic cancers. Against central nervous system (CNS) tumors, CAR T cells targeting B7-H3, a protein highly expressed on DIPG, have rapidly advanced from preclinical studies to clinical trials. BrainChild-03 (NCT04185038), a phase 1 trial of repeatedly delivered intracerebroventricular (ICV) B7-H3-targeting CAR T cells (B7-H3 CAR T cells), demonstrated tolerability and potential efficacy for children and young adults with DIPG. However, clinical benefits were not uniformly seen, and multi-agent treatment strategies may be required against such an aggressive disease. Here, we combined B7-H3 CAR T cells with ONC206, an imipridone molecule also under clinical investigation.

Methods:

We tested B7-H3 CAR T cells combined with ONC206 across multiple DIPG cell cultures and orthotopic xenograft mouse models.

Results:

B7-H3 CAR T cell monotherapy induced robust cytotoxicity while ONC206 treatment resulted in significant mitochondrial dysfunction against DIPG cells. The combination of low effector-to-target ratios of B7-H3 CAR T cells and IC50 concentrations of ONC206 led to significantly enhanced cytotoxicity in vitro (P < .003) and increased IL-2, IL-29, VEGF-A, and Granzyme B levels. In vivo combinatorial studies of ONC206 and a single ICV dose of B7-H3 CAR T cells extended survival in DIPG xenograft mouse models.

Conclusions:

B7-H3 CAR T cells combined with ONC206 are a feasible and efficacious multi-agent approach against multiple DIPG models.

01 Mar 2026·Journal for ImmunoTherapy of Cancer

RASA2 deletion rescues immune synapse dysfunction, enhancing CAR T cell efficacy against DMGs

Article

Author: Ocasio, Jennifer K ; Odde, David ; Teis, Robert ; Mehta, Sanya ; Baker, Suzanne ; Krenciute, Giedre ; Allo Anido, Alejandro ; Ward, Meghan ; Meehl, Michaela ; Ibanez-Vega, Jorge ; Ansari, Aamir ; Chockley, Peter ; Prinzing, Brooke

Background:

Chimeric antigen receptor (CAR) T-cell therapy has demonstrated safety and modest efficacy against diffuse midline gliomas (DMGs), a highly aggressive pediatric brain tumor. However, mechanisms of CAR T-cell resistance in DMG settings remain unknown.

Methods:

We compared the efficacy of B7-H3 CAR T-cells between SJ-DIPGX7c (DMG) and U87-MG (adult glioblastoma) patient-derived cell lines and showed impaired efficacy both in vitro and in vivo. We performed live-cell imaging and single-cell RNA sequencing to investigate deficiencies in immune synapse (IS) formation between CAR T-cells and DMGs. Lastly, we genetically deleted RASA2 , a negative regulator of T cell activation, and evaluated the resulting impact on IS formation and quality, as well as in vitro and in vivo functionality.

Results:

We show that limited efficacy of B7-H3 CAR T-cells is due to DMG-mediated inefficient interaction between CAR T-cells and DMG cells. Specifically, DMG cells impair the IS formation, resulting in poor CAR T-cell activation, cytokine secretion, and limited anti-tumor response in vivo. RASA2 deletion improved CAR T-cell activation through the formation of a more functional IS. RASA2-deleted CAR T-cells exhibited enhanced calcium flux, increased accumulation of activated signaling molecules and lytic granules at the synapse, and increased actin cytoskeleton dynamics, which produced larger synaptic areas and resulted in enhanced migration ex vivo. Further, RASA2-deleted CAR T-cells demonstrated improved in vitro functionality and superior early in vivo anti-tumor responses against DMGs compared with controls.

Conclusions:

Our study highlights the importance of understanding tumor-specific factors that limit CAR T-cell response and using this information to design superior next-generation CAR T-cells. Specifically, we identify cytoskeleton remodeling and T cell motility as therapeutically actionable targets for future engineering approaches.

19 Oct 2025·BRITISH JOURNAL OF CANCER

The pronounced cytotoxic effects of chimeric antigen receptor T cells targeting B7-H3 in organoids and liver xenografts derived from colorectal cancer patients

Article

Author: Xiao, Yanlin ; Chang, Yanyun ; Wei, Wenqing ; Liu, Qi ; Sheng, Yuling ; Gao, Jing ; Yan, Li ; Tan, Jingyun ; Du, Changzheng ; Li, Wenhua ; Tan, Yi ; Peng, Yifan ; Cao, Linlin ; Zhang, Wenyong ; Mao, Wei ; Xu, Yang

Abstract:

Background:

The application of chimeric antigen receptor (CAR)-T cells in solid tumors is hindered due to the lack of specific tumor antigen and limited clinical efficacy. Our aim is to develop and validate novel CAR-T cell therapy against metastatic colorectal cancer (CRC).

Methods:

By analyzing the expression of B7-H3 in CRC tissue and cell lines using immunohistochemistry (IHC) and flow cytometry, respectively, we identified B7-H3 as a potential target in CRC. We thereby developed CAR-T cells targeting B7-H3 (B7-H3 CAR-T) and evaluated their anti-tumor activity in vitro and in vivo, using patient-derived organoids (PDOs) and xenograft (PDX) models to validate its translational potential.

Results:

In our cohort of 170 CRC patients, B7-H3 was significantly upregulated in CRC tumors compared to paratumor tissue, as determined by IHC staining. When co-cultured with CRC cells or PDOs, B7-H3 CAR-T cells exhibited a dose-dependent cytotoxicity in vitro. Furthermore, B7-H3 CAR-T cells effectively controlled tumor growth and metastasis in vivo, significantly prolonging survival time for the tumor-burden mice through cytotoxic killing and potential immune regulatory effects, demonstrated in both CRC cell-based and PDX-based metastatic models.

Conclusions:

These findings underscore the potential efficacy of B7-H3 CAR-T cells for treating metastatic CRC and highlight its translational value.

100 Deals associated with B7-H3-CAR T cells(St. Jude Children's Research Hospital)

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Childhood Rhabdomyosarcoma	Phase 1	United States	St. Jude Children's Research Hospital, Inc.	21 Jan 2026
Diffuse midline glioma, point mutation K27M in histone H3	Phase 1	United States	St. Jude Children's Research Hospital, Inc.	27 Apr 2023
Ependymoma	Phase 1	United States	St. Jude Children's Research Hospital, Inc.	27 Apr 2023
Glioblastoma	Phase 1	United States	St. Jude Children's Research Hospital, Inc.	27 Apr 2023
High grade glioma	Phase 1	United States	St. Jude Children's Research Hospital, Inc.	27 Apr 2023
Medulloblastoma	Phase 1	United States	St. Jude Children's Research Hospital, Inc.	27 Apr 2023
Teratoid Tumor, Atypical	Phase 1	United States	St. Jude Children's Research Hospital, Inc.	27 Apr 2023
Adrenal Cortex Neoplasms	Phase 1	United States	St. Jude Children's Research Hospital, Inc.	06 Jul 2022
Carcinoma	Phase 1	United States	St. Jude Children's Research Hospital, Inc.	06 Jul 2022
Clear Cell Sarcoma	Phase 1	United States	St. Jude Children's Research Hospital, Inc.	06 Jul 2022

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