NCT07321301

Polymer-lipid Particle-delivered CAR1920 mRNA CAR-T Therapy for Relapsed/Refractory B-cell Lymphoma/Leukemia

An Exploratory Clinical Study of CAR-T Cell Immunotherapy Using Polymer-lipid Particles to Deliver CAR1920 mRNA Targeting CD19/CD20 for Thetreatment of Relapsed/Refractory B-cell Lymphoma/Leukemia

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Sponsor: Daihong Liu · Academic / Other
• Sex: All
• Age: 14 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine the efficacy and safety of the CAR-T cell immunotherapy utilizing polymer-lipid nanoparticles for delivering CD19/CD20 dual-targeting InViVoCAR1920 mRNA, for the first-line consolidation therapy of relapsed/refractory B-cell lymphoma/leukemia.

Detailed description

Since 2010, Chimeric Antigen Receptor T-Cell Immunotherapy (CAR-T Cell Immunotherapy) has demonstrated excellent targeting, cytotoxicity, and durability in tumor treatment, achieving well-recognized clinical efficacy in hematological malignancies. CAR-T Cell Immunotherapy refers to a technique that uses genetic modification to introduce genetic material encoding a specific antigen-recognition domain and T-cell activation signals into T cells. These engineered T cells are activated by direct binding to specific antigens on the surface of tumor cells, directly killing tumor cells through the release of perforin, granzyme B, etc. Simultaneously, they recruit endogenous immune cells in the human body to eliminate tumor cells by secreting cytokines, thereby achieving tumor treatment. Furthermore, they can form memory T cells to establish a specific and long-term anti-tumor mechanism.CD19 and CD20 are specific markers of B-cell malignancies, widely expressed in various B-cell malignant tumors. However, single-antigen targeting is prone to inducing antigen escape, as tumor cells often evade recognition and attack by CAR-T cells by losing or downregulating the expression of a single target antigen. Nevertheless, it is relatively difficult for tumor cells to alter the expression of two antigens simultaneously. For example, 70% of patients who relapse after CD19 CAR-T therapy exhibit loss of CD19 expression, a population that can be covered by CD20 CAR-T therapy. However, the efficacy of single-agent therapy is still limited by antigen heterogeneity. Dual-target CAR-T cells simultaneously target CD19 and CD20 antigens. Even if tumor cells escape via one antigen, they can still exert cytotoxic effects through recognition of the other antigen, thereby significantly reducing the risk of antigen escape, improving tumor clearance efficiency, and lowering the recurrence rate.Lipid Nanoparticles (LNPs) are composed of cationic lipids, helper lipids, cholesterol, and polyethylene glycol (PEG)-modified lipids. They can efficiently encapsulate mRNA to form stable nanoscale particle structures, effectively protecting mRNA from degradation by nucleases in the body. Through interaction with the cell surface, LNPs can precisely deliver mRNA into T cells, enabling transient expression of CAR proteins and in situ generation of CAR-T cells. This technology eliminates the need for ex vivo cell manipulation, significantly shortening the treatment cycle and allowing patients to receive therapy more quickly. Meanwhile, it avoids the potential T-cell exhaustion that may occur during ex vivo T-cell expansion, improving the yield of effective therapeutic products.

Conditions

• B-cell Lymphoma Refractory

Interventions

Type	Name	Description
DRUG	Polymer-Lipid Nanoparticle-Mediated Delivery of CD19/CD20 Dual-Targeting InViVoCAR1920 mRNA for CAR-T Cell Immunotherapy	Polymer-Lipid Nanoparticle-Mediated Delivery of CD19/CD20 Dual-Targeting InViVoCAR1920 mRNA for CAR-T Cell Immunotherapy in the Treatment of Patients with Relapsed/Refractory (R/R) B-Cell Lymphoma/Leukemia

Timeline

• Start date: 2025-09-01
• Primary completion: 2027-08-31
• Completion: 2027-08-31
• First posted: 2026-01-07
• Last updated: 2026-01-07

Locations

1 site across 1 country: China