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Review
. 2025 Mar 4:16:1490491.
doi: 10.3389/fimmu.2025.1490491. eCollection 2025.

CD19 -targeted CAR T therapy treating hematologic malignancies: hidden danger is the next neighbor to security?

Xueshuai Ye  1 , Min Ge  1 , Mengtian Tan  1 , Yongqiang Wu  2 , Haiqiang Zhang  3 , Zexian Fu  4
Affiliations
Review

CD19 -targeted CAR T therapy treating hematologic malignancies: hidden danger is the next neighbor to security?

Xueshuai Ye et al. Front Immunol. .

Abstract

CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has achieved marvelous results in the treatment of patients with relapsed and/or refractory B-cell lymphomas, B-cell acute lymphoblastic leukemia, and multiple myeloma. As a new treatment method that has changed the existing treatment paradigm, there has been a short time from its emergence to FDA approval. However, with the increasing number of cases and the passage of time, hidden problems have gradually been exposed. In this review, we summarize the short- and long-term toxicity, such as secondary T-cell tumors and lethal CAR tumors, of patients with hematologic malignancies treated with CD19-CAR-T cells, including cytokine release syndrome (CRS), ICANS, and secondary malignancies with low occurrence rates but high mortality, such as secondary T cell tumors and lethal CAR tumors, which may be related to the gene modification mechanism of viral vectors currently approved for CAR-T cells. We also discuss potential investigational strategies designed to improve the safety of CAR-T-cell therapy.

Keywords: CAR T cancer therapy; CD19; cytokine release syndrome (CRS); immune effector cell-associated neurotoxicity syndrome (ICANS); secondary malignancies.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic diagram of CD19-CAR T associated side effects.
Figure 2
Figure 2
Schematic diagram of CD19-CAR T clearing B malignant cells and B cell CD19 antigen loss mechanism. (A) CD19 CAR recognition of the CD19 binding site and intiation of tumor celarance. (B) Cancer cell phenotypie switch to CD19 negative. (C) CD19-CAR masking to CD19 binding site.
Figure 3
Figure 3
Technical schematic diagram for preparing CD19-CAR T by infecting T cells with lentivirus vector.
Figure 4
Figure 4
Technical schematic diagram for preparing CD19-CAR T malignant cells by infecting T cells with lentivirus vector.
Figure 5
Figure 5
The mechanism of CAR T cells production process involves the contamination of raw T cells by B malignant cells, leading to the fatal of CAR B production.
Figure 6
Figure 6
The mechanism of hidden CD19 antigen by CD19 CAR receptor expressed in lentivirus infected malignant B cells.
See this image and copyright information in PMC

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