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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
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
Chinese PLA General Hospital
Beijing, Beijing Municipality, China
RECRUITINGthe safety and maximum tolerated dose of CAR-T cell immunotherapy mediated by polymer-lipid nanoparticles delivering CD19/CD20 dual-targeting InViVoCAR1920 mRNA in patients with relapsed/refractory B-cell lymphoma/leukemia
Time frame: 3 months after treatment
30-day response rate
30-day response rate refers to the proportion of patients who achieve complete or partial response from the start of treatment.
Time frame: 30 days
90-day response rate
90-day response rate refers to the proportion of patients who achieve complete or partial response 90 days after the start of treatment.
Time frame: 90 days
overall survival (OS)
Overall survival (OS) refers to the time from the start of treatment to the death of the patient for any reason
Time frame: 6 months after treatment
progression free survival (PFS)
Progression free survival (PFS) refers to the time from treatment to the first myeloma progression or death of the patient for any reason.
Time frame: 6 months after treatment
time to progression (TTP)
Time to progression (TTP) refers to the time from treatment to the first myeloma progression.
Time frame: 6 months after treatment
disease free survival (DFS)
Disease free survival (DFS) refers to the time from treatment to the first myeloma recurrence.
Time frame: 3 months after treatment
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duration of response (DOR)
Duration of Response (DOR) refers to the time from the first assessment of a myeloma as a complete or partial response to the first assessment of PD (Progressive Disease) or death from any cause.
Time frame: 6 months after treatment
event free survival (EFS)
Event Free Survival (EFS) is a commonly used endpoint indicator in clinical trials to evaluate the survival time of patients without any adverse events during a specific time period. These adverse events include but are not limited to disease progression, death, treatment plan changes, and the occurrence of serious side effects.
Time frame: 6 months after treatment
recurrence rate
The recurrence rate refers to the proportion of patients with lymphoma recurrence after treatment.
Time frame: 3 months after treatment