NCT06696846

CD70-CAR-NK Cell Therapy for T Cell Lymphoma and Acute Myeloid Leukemia

Cord Blood-derived CD70-targeting CAR-NK Cell Therapy for Refractory/relapsed T Cell Lymphoma and Acute Myeloid Leukemia

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 25 (estimated)
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

CD70 is a promising target for immunotherapy because it is overexpressed in T-cell lymphoma (TCL) and acute myeloid leukemia (AML) tumor cells but is found in deficient levels in normal tissues and hematopoietic stem cells. This study aims to evaluate the safety and efficacy of CD70-targeted CAR-NK (CD70-CAR-NK) cells in patients with relapsed and refractory TCL and AML.

Detailed description

Despite significant advances in CAR-T cell therapy for refractory and relapsed B-cell malignancies and multiple myeloma, CAR-T therapy for T cell lymphoma and acute myeloid leukemia only resulted in suboptimal response partly due to the lack of an ideal target and possible fratricide. Chimeric antigen receptor (CAR)-NK cells may have advantages over CAR-T cells, such as reducing cytokine release and preventing fratricide and tumor contamination in T-cell lymphoma. CD70, which is overexpressed in tumor cells in T cell lymphoma and AML but minimally in normal tissues or hematopoietic stem cells, has emerged as a novel immunotherapy target. Inhibition of the growth of CD70-positive tumors through blocking the CD70/CD27 pathway potentially led to clinical response in relapsed/refractory T-cell lymphoma and AML. In preclinical studies, we and others have shown that CD70 CAR-NK cells effectively suppress the growth of lymphoma and AML xenograft in vivo, extending the survival of tumor-bearing mice but without significant toxicities. This study aims to evaluate the safety, pharmacokinetics, and efficacy of CD70-targeted CAR-NK cells in patients with CD70-positive relapsed/refractory T-cell lymphoma and AML.

Conditions

• Relapsed/refractory T-cell Lymphoma
• Relapsed/refractory Acute Myeloid Leukemia

Interventions

Type	Name	Description
BIOLOGICAL	CD70 CAR-NK	CAR - NK cells constructed by using genetic engineering technology retain the original extensive tumor - killing ability of NK cells. By using their unique target cell recognition mechanism, the target is accurately locked on specific antigen proteins, thereby enhancing the anti - tumor effect. Cord blood-derived CAR - NK cell products shorten the treatment time and are inexpensive. Multiple studies have confirmed the feasibility of CAR - NK cells in treating hematological tumors. Blocking the CD70/CD27 signaling pathway plays an important role in inhibiting CD70 - positive tumors, such as refractory/relapsed T - cell lymphoma and acute myeloid leukemia. Pre - clinical studies in our laboratory have proved that CD70 CAR - NK can effectively inhibit the in - vivo and in - vitro proliferation of T - cell lymphoma and prolong survival.

Timeline

• Start date: 2024-12-01
• Primary completion: 2027-11-30
• Completion: 2028-11-30
• First posted: 2024-11-20
• Last updated: 2024-11-20