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Updated: Jan 29, 2026
In Ovo Xenografting of Patient-Derived Acute Lymphoblastic Leukemia (ALL) Cells (PDX-ALL)
Published on: August 1, 2025
A novel CD7 chimeric antigen receptor-modified NK-92MI cell line targeting T-cell acute lymphoblastic leukemia
Fengtao You1,2,3, Yinyan Wang3, Licui Jiang3
1The Cyrus Tang Hematology Center, Soochow University Suzhou, Jiangsu, P. R. China.
Abstract:
Chimeric antigen receptor (CAR) immunotherapy has recently shown promise in clinical trials for B-cell malignancies; however, designing CARs for T-cell based diseases remain a challenge since most target antigens are shared between normal and malignant cells, leading to CAR-T cell fratricide. CD7 is highly expressed in T-cell acute lymphoblastic leukemia (T-ALL), but it is not expressed in one small group of normal T lymphocytes. Here, we constructed monovalent CD7-CAR-NK-92MI and bivalent dCD7-CAR-NK-92MI cells using the CD7 nanobody VHH6 sequences from our laboratory. Both CD7-CAR-NK-92MI and dCD7-CAR-NK-92MI cells consistently showed specific and potent anti-tumor activity against T-cell leukemia cell lines and primary tumor cells. We observed robust cytotoxicity of the bivalent mdCD7-CAR-NK-92MI monoclonal cells against primary T-ALL samples. In agreement with the enhanced cytotoxicity of mdCD7-CAR-NK-92MI cells, significant elevations in the secretion of Granzyme B and interferon γ (IFN-γ) were also found in mdCD7-CAR-NK-92MI cells in response to CD7-positive primary T-ALL cells compared with NK-92MI-mock cells. Furthermore, we also demonstrated that mdCD7-CAR-NK-92MI cells significantly inhibited disease progression in xenograft mouse models of T-ALL primary tumor cells. Our data suggest that CD7-CAR-NK-92MI cells can be used as a new method or a complementary therapy for treating T-cell acute lymphocytic leukemia.
Insights
This study developed novel CD7-CAR-NK-92MI cells to combat T-cell acute lymphoblastic leukemia (T-ALL). These engineered cells demonstrated potent anti-tumor activity in vitro and in vivo, offering a promising new therapeutic strategy for T-ALL.
Area of Science:
- Immunotherapy
- Oncology
- Cell Biology
Background:
- Chimeric antigen receptor (CAR) immunotherapy shows promise for B-cell malignancies but faces challenges in T-cell diseases due to antigen sharing and CAR-T cell fratricide.
- CD7 is a highly expressed antigen in T-cell acute lymphoblastic leukemia (T-ALL), with limited expression on normal T cells, making it a potential therapeutic target.
Purpose of the Study:
- To construct and evaluate the efficacy of monovalent and bivalent CD7-CAR-NK-92MI cells for treating T-cell malignancies.
- To assess the anti-tumor activity, cytokine secretion, and in vivo therapeutic potential of CD7-CAR-NK-92MI cells against T-ALL.
Main Methods:
- Construction of monovalent CD7-CAR-NK-92MI and bivalent dCD7-CAR-NK-92MI cells using CD7 nanobody VHH6 sequences.
- In vitro assessment of cytotoxicity against T-cell leukemia cell lines and primary T-ALL cells.
- Measurement of Granzyme B and interferon-gamma (IFN-γ) secretion.
- Evaluation of therapeutic efficacy in xenograft mouse models of T-ALL.
Main Results:
- Both CD7-CAR-NK-92MI and dCD7-CAR-NK-92MI cells exhibited specific and potent anti-tumor activity.
- Bivalent mdCD7-CAR-NK-92MI cells showed robust cytotoxicity against primary T-ALL samples.
- Enhanced secretion of Granzyme B and IFN-γ was observed with mdCD7-CAR-NK-92MI cells.
- mdCD7-CAR-NK-92MI cells significantly inhibited T-ALL progression in xenograft mouse models.
Conclusions:
- CD7-CAR-NK-92MI cells, particularly the bivalent form, demonstrate significant potential as a therapeutic strategy for T-cell acute lymphoblastic leukemia.
- These engineered NK cells offer a promising new method or complementary therapy for T-ALL treatment, overcoming challenges associated with CAR-T cell fratricide.
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