4SCAR-T Therapy Targeting GD2, PSMA and CD276 for Treating Neuroblastoma

Study Purpose

The purpose of this clinical trial is to assess the feasibility, safety and efficacy of multiple 4SCAR-T cell therapy which targets GD2, PSMA and CD276 surface antigens in patients with relapsed and refractory neuroblastoma (NB). Another goal of the study is to understand the function of the multi-CAR-T cells and their persistency in the patients.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.

An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.

Searching Both is inclusive of interventional and observational studies.

Eligible Ages 1 Year - 65 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Patients with tumors have received standard first-line therapy and been judged to be non-resectable, metastatic, progressive or recurrent.
  • - The expression status of GD2, PSMA and CD276 antigens of the tumor will be determined for eligibility.
Positive expression is defined by GD2, PMSA and CD276 antibody staining results based on immunohistochemistry or flow cytometry analyses.
  • - Body weight greater than or equal to 10 kg.
  • - Age: ≥1 year and ≤ 65 years of age at the time of enrollment.
  • - Life expectancy: at least 8 weeks.
  • - Prior Therapy: 1.
There is no limit to the number of prior treatment regimens. Any grade 3 or 4 non-hematologic toxicity of any previous therapy must have resolved to grade 2 or less. 2. Participant must not have received hematopoietic growth factors for at least 1 week prior to mononuclear cells collection. 3. At least 7 days must have elapsed since the completion of therapy with a biologic agent, targeted agent, tyrosine kinase inhibitor or a metronomic non-myelosuppressive regimen. 4. At least 4 weeks must have elapsed since prior therapy that included a monoclonal antibody. 5. At least 1 week since any radiation therapy at the time of study entry.
  • - Karnofsky/jansky score of 60% or greater.
  • - Cardiac function: Left ventricular ejection fraction greater than or equal to 40/55 percent.
  • - Pulse Ox greater than or equal to 90% on room air.
  • - Liver function: defined as alanine transaminase (ALT) <3x upper limit of normal (ULN), aspartate aminotransferase (AST) <3x ULN; serum bilirubin and alkaline phosphatase <2x ULN.
  • - Renal function: Patients must have serum creatinine less than 3 times upper limit of normal.
  • - Marrow function: White blood cell count ≥1000/ul, Absolute neutrophil count ≥500/ul, Absolute lymphocyte count ≥500/ul, Platelet count ≥25,000/ul (not achieved by transfusion).
  • - Patients with known bone marrow metastatic disease will be eligible for study as long as they meet hematologic function criteria, and the marrow disease not evaluable for hematologic toxicity.
  • - For all patients enrolled in this study, their parents or legal guardians must sign an informed consent and assent.

Exclusion Criteria:

  • - Existing severe illness (e.g. significant cardiac, pulmonary, hepatic diseases, etc.) or major organ dysfunction, with the exception of grade 3 hematologic toxicity.
  • - Untreated central nervous system (CNS) metastasis: Patients with previous CNS tumor involvement that has been treated and is stable for at least 6 weeks following completion of therapy are eligible.
  • - Previous treatment with other genetically engineered GD2, PSMA and CD276 CART cells.
  • - Active HIV, Hepatitis B virus (HBV), Hepatitis C virus (HCV) infection or uncontrolled infection.
  • - Patients who require systemic corticosteroid or other immunosuppressive therapy.
  • - Evidence of tumor potentially causing airway obstruction.
  • - Inability to comply with protocol requirements.
  • - Insufficient CART cells availability.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.


Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Shenzhen Geno-Immune Medical Institute
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Overall Status Recruiting
Countries China

The disease, disorder, syndrome, illness, or injury that is being studied.

Additional Details

Neuroblastoma is one of the most aggressive childhood tumors arising from neural crest cells. Nearly 50% of patients with high risk disease have poor long-term survival even after multimodal treatments. Novel immunotherapy targeting tumor-specific antigens has been developed to meet the desperate need. Disialoganglioside (GD2) is a well-studied tumor associated antigen which is expressed uniformly in NB but restrictedly in normal tissue. Over the past few years, CAR-T therapy against GD2 in NB has achieved encouraging but modest outcomes. Only a fraction of patients achieved measurable responses. Like for many other solid tumors, CAR-T therapy for NB is not as effective as for hematologic malignancies. In this study, the investigators use "multiple targeting" approach as the strategy to overcome the challenge in treating NB. Prostate-specific membrane antigen (PSMA) is expressed in normal prostate but is upregulated in prostate tumor. However, PSMA expression is not restricted to prostate cancer. By immunohistochemistry (IHC) staining, the investigators confirmed that PSMA is expressed in a variety of solid tumors, including brain tumor, neuroblastoma and some lymphoma tumor tissues. Therefore, PSMA could potentially serve as a promising target for antigen-specific immunotherapy in patients with NB. In addition, CD276 (B7-H3) is an immune checkpoint molecule highly expressed on many solid tumors including NB. CD276 has been characterized to be involved in tumor evasion and thus its expression is correlated with poor prognosis. These characteristics make CD276 an attractive candidate for immunotherapy. Given the significant variation of tumor antigen expression among patients, the investigators aim to examine GD2, PSMA and CD276 expression in each patient's tumor sections by IHC staining, and combine two or three highly-expressed targets for the 4SCAR-T therapy. This individualized and multi-antigen-targeted approach is a new strategy to overcome the limited clinical outcome in the 4SCAR-T therapy against NB. The purpose of this clinical study is to assess the feasibility, safety and efficacy of the combinational GD2, PSMA and CD276 4SCAR-T cell therapy against NB. Another goal of the study is to learn more about the function of the multi-4SCAR-T cells and their persistency in the patients.

Arms & Interventions


Experimental: effectiveness of CAR-T cells targeting GD2, PSMA and CD276

Gene-modified T cells are designed to kill tumor cells through specific recognition of GD2, PSMA and CD276. This study will evaluate the side effects and effective doses of GD2, PSMA and CD276 CAR-T cells in treating refractory and recurrent NB


Biological: - GD2, PSMA and CD276 CAR-T cells

infusion, for 1x10^6~1x10^7 cells/kg via IV

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Guangzhou, Guangdong, China




Guangdong Zhujiang Hospital of Southern Medical University

Guangzhou, Guangdong, 510282

Site Contact

Lihua Yang, M.D, PhD



Shenzhen Children's Hospital, Shenzhen, Guangdong, China




Shenzhen Children's Hospital

Shenzhen, Guangdong, 518000

Site Contact

Xiuli Yuan, M.D



Shenzhen Geno-Immune Medical Institute, Shenzhen, Guangzhou, China




Shenzhen Geno-Immune Medical Institute

Shenzhen, Guangzhou, 518000

Site Contact

Lung-Ji Chang, PhD



Shandong Cancer Hospital, Jinan, Shandong, China




Shandong Cancer Hospital

Jinan, Shandong, 250022

Site Contact

Jingfu Wang, M.D, Ph.D



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