B-cell lymphomas are a group of malignant hematologic malignancies originating from B lymphocytes, including subtypes such as diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). Although first-line immunochemotherapy (such as R-CHOP) can achieve remission in some patients, a significant proportion of patients experience disease relapse or become unresponsive to multiple lines of therapy (refractory). Refractory/relapsed B-cell lymphomas typically progress rapidly, have a poor prognosis, posing significant challenges for clinical treatment.

Currently, main treatment options for refractory/relapsed B-cell lymphoma include salvage chemotherapy combined with autologous hematopoietic stem cell transplantation, monoclonal antibodies or antibody-drug conjugates, small molecule targeted therapy, and traditional CAR-T cell therapy. However, these treatment methods still have significant limitations in clinical application. For example, repeated chemotherapy can easily lead to drug resistance accumulation; high-intensity treatment places high demands on the patient's physical condition, and some patients cannot tolerate it; the duration of remission from targeted drugs and antibody therapies is limited; and traditional CAR-T therapy may still cause problems such as insufficient T cell proliferation, limited persistence, and disease relapse in some patients.

The fourth-generation CAR-T cells that target CD19 and secrete interleukin-7 (IL-7) and the chemokine CCL19 can systematically overcome the treatment bottlenecks of traditional anti-CD19 CAR-T therapy. IL-7 is a key cytokine for maintaining T cell survival and promoting their proliferation, and can significantly enhance the in vivo proliferation capacity and long-term persistence of CAR-T cells, thereby maintaining a stable and durable anti-tumor effect. Simultaneously, CCL19 can effectively recruit endogenous T cells and dendritic cells into the tumor microenvironment, promoting the synergistic effect of CAR-T cells and the host immune system, and enhancing the local anti-tumor immune response.

This clinical study is currently recruiting eligible patients with refractory/relapsed B-cell lymphoma to receive treatment with IL-7 and CCL19-expressing CD19-CAR-T cell therapy.

Treatment Protocol

Intervention Overview

This Phase 2 interventional study evaluates IL-7 and CCL19-expressing CD19-CAR-T therapy in patients with refractory or relapsed B cell lymphoma. The therapy uses autologous T cells genetically engineered to target CD19 on malignant B cells while simultaneously expressing Interleukin-7 (IL-7) and Chemokine (C-C motif) ligand 19 (CCL19).

• Enhanced T cell proliferation and persistence (IL-7), enabling sustained anti-tumor activity.
• Immune cell recruitment (CCL19), which attracts endogenous T cells and dendritic cells to the tumor site, promoting a coordinated immune response.
• Selective targeting of CD19-positive B cells, ensuring effective elimination of malignant cells.

This muti-function design is intended to improve therapeutic efficacy, overcome tumor immune evasion, and provide durable responses for patients with refractory B cell lymphomas.

Fourth-Generation Anti-CD19 CAR-T with IL-7/CCL19 Enhancement

Treatment Process

• Screening and Enrollment

Patients undergo a comprehensive screening process, including disease status evaluation, laboratory testing, organ function assessment, and confirmation of eligibility according to the study criteria.

• CAR-T Cell Manufacturing

Autologous T cells are collected from the patient and genetically engineered ex vivo to express a CD19-targeted chimeric antigen receptor (CAR) along with inducible IL-7 and CCL19. The modified CAR-T cells are then expanded under controlled conditions to achieve the required therapeutic dose.

• CAR-T Cell Infusion

Following lymphodepleting chemotherapy, patients receive a single intravenous infusion of IL-7 and CCL19-expressing CD19 CAR-T cells, with the dose administered according to the clinical trial protocol.

• Monitoring and Follow-Up

Patients are closely monitored for treatment-related toxicities, including cytokine release syndrome (CRS) and neurotoxicity. Disease response and CAR-T cell persistence are evaluated through laboratory tests, imaging, and bone marrow assessments at predefined time points.

Patient Recruitment Criteria

• Hi-TCR-T Treatment for Solid Tumors
• HLA-Independent TCR-T for Refractory Multiple Myeloma
• Multi-Target Hi-TCR-T for Hepatocellular Carcinoma
• Fourth-Generation Nectin4/FAP-Targeted CAR-T for Malignant Solid Tumors