GD2/CD70 Bi-specific CAR-T Cell Therapy

  • STATUS
    Recruiting
  • End date
    Jun 30, 2026
  • participants needed
    30
  • sponsor
    Shenzhen Geno-Immune Medical Institute
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Updated on 10 July 2022
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Summary

The purpose of this study is to assess the feasibility, safety and efficacy of GD2/CD70 bi-specific CAR-T cell therapy in patients with GD2 and/or CD70 positive tumor. Another goal of the study is to learn more about the function of the GD2/CD70 bi-specific CAR-T cells and their persistency in patients.

Description

Patients with refractory and/or recurrent cancer may have poor prognosis despite complex multimodal therapy; therefore, novel curative approaches are needed. The investigators attempt to use T cells genetically modified to express a 4th generation lentiviral anti-GD2/CD70 bi-specific chimeric antigen receptor (bi-4SCAR-GD2/CD70). The chimeric antigen receptor (CAR) molecules enable the T cells to recognize and kill target cells through the recognition of a surface antigen, GD2 or CD70, which is expressed at high levels on cancer cells but not at significant levels on normal tissues.

Disialoganglioside (GD2) is a well-studied tumor associated antigen which is expressed uniformly in nervous system-related tumors but at low levels in normal tissues. Over the past few years, CAR-T therapy against GD2 in tumor has achieved encouraging but modest outcomes. Only a fraction of patients achieved measurable responses. In solid tumors, GD2 CAR-T therapy alone may not be as effective as CAR-T cell therapy in hematological malignancies.

CD70 is a promising therapeutic target due to its restricted expression in normal tissues and overexpression in malignant tissues. Expression of CD70 was observed on multiple tumor types including kidney, breast, esophageal, liver, colon cancer, glioma, hepatoma as well as melanoma. In addition, it has been reported that anti-CD70 CAR T-cells eliminated CD70-positive cells and had strong anti-tumor effects in preclinical animal models. The CD70 targeted CAR-T cells with binding moiety of CD70 specific scFv exhibited a higher affinity and antitumor effect against CD70+ tumor cells. A potential strategy to prevent relapse due to antigen escape is to infuse T-cells capable of recognizing multiple antigens.

To overcome escape of single target antigen in tumor cells and to enhance in vivo CAR-T efficacy, a novel bi-specific GD2/CD70 CAR-T therapy regimen is developed to include booster and consolidation CAR-T applications to target highly-refractory cancer. The aim is to evaluate safety and long term efficacy of the bi-CAR-T therapy strategy in GD2 and/or CD70 positive cancer patients.

Details
Condition Cancer Disease
Treatment bi-4SCAR GD2/CD70 T cells
Clinical Study IdentifierNCT05438368
SponsorShenzhen Geno-Immune Medical Institute
Last Modified on10 July 2022

Eligibility

 Yes No Not Sure

Inclusion Criteria

Patients with tumors received standard first-line therapy and judged to be non-resectable, metastatic, progressive or recurrent
The expression status of GD2 or CD70 antigens in the tumor tissue will be determined for eligibility. Positive expression is defined by GD2 and PMSA antibody staining results based on immunohistochemistry or flow cytometry analyses
Body weight greater than or equal to 10 kg
Age: ≥1 year and ≤ 75 years of age at the time of enrollment
Life expectancy: at least 8 weeks
Prior Therapy
There is no limit to the number of prior treatment regimens. Any grade 3 or 4
non-hematologic toxicity of any previous therapy must be resolved to grade 2
or less
Participant must not have received hematopoietic growth factors for at least 1 week prior to mononuclear cells collection
At least 7 days must have elapsed since the completion of therapy with a biologic agent, selected targeted agent or a metronomic non-myelosuppressive regimen
At least 4 weeks must have elapsed since prior therapy that included a monoclonal antibody
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 does not have hematologic toxicity
For all patients enrolled in this study, themselves or 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, or greater than grade 2 hematologic toxicity
Untreatable 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 or CD70-specific CAR T 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 CAR T cells availability
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