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Hung Trinh Shared New Study on CAR-T Therapy Targeting TNF in AML and Solid Tumors

Hung Trinh/LinkedIn

Aug 17, 2025, 14:15

Hung Trinh Shared New Study on CAR-T Therapy Targeting TNF in AML and Solid Tumors

Hung Trinh, Senior VP of Operations at Seneca Therapeutics, shared a post on LinkedIn about a recent article by Takahiro Nakashima at al. published in the Journal for ImmunoTherapy of Cancer:

“JAK-STAT-activated, fratricide-resistant CAR-T cells targeting membrane-bound TNF effectively treat AML and solid tumors

Results TNF-NTF CAR-T cells efficiently lysed TNF-expressing leukemia cells in vitro, while showing limited antitumor efficacy in vivo due to poor expansion and persistence. Activated T cells upregulate TNF, which was recognized by TNF-NTF CAR-T cells and led to fratricide. Genetic knockout (KO) of TNF significantly enhanced the viability and proliferation of TNF-NTF CAR-T cells, while slightly reducing their cytotoxic activity. In addition, ectopic expression of G6/7R improved the effector function of TNF-NTF CAR-T cells through constitutive activation of janus kinase (JAK)-signal transducers and activators of transcription (STAT) signaling. The G6/7R–expressing TNF-KO TNF-NTF CAR-T cells exhibited superior persistence and durable antileukemic efficacy in vivo compared with parental CAR-T cells.

We also confirmed that TNF-NTF CAR-T cells can target primary AML cells, including a leukemia-initiating population with colony-forming capacity. Unlike CD33, targeting TNF-NTF did not show cytotoxicity against normal hematopoietic stem/progenitor cells. Finally, we demonstrated the curative efficacy of G6/7R TNF-KO TNF-NTF CAR-T cells against TNF-expressing ovarian tumor cells in vivo.

The role of tumor-derived TNF has also been reported in the progression of epithelial cancers such as head and neck tumors and gastrointestinal tumors. In addition, a recent study has reported the potential efficacy of TNF-targeting CAR-T cells against breast cancer cells when combined with PD-L1 blockade. TNF is also expressed in myeloid-derived suppressor cells and macrophages in the solid tumor microenvironment and contributes to their immunosuppressive functions.50 Investigations in immunocompetent tumor models will be necessary to evaluate the consequences of targeting TNF on the immune microenvironment.

In conclusion, our studies highlight TNF-NTF as a promising cell surface target for CAR-T cell therapy that can be applied to AML as well as solid tumors. Future studies are warranted to establish a method to accurately identify cases that can be effectively targeted by the TNF-NTF CAR-T cells.”

Title: JAK-STAT-activated, fratricide-resistant CAR-T cells targeting membrane-bound TNF effectively treat AML and solid tumors

Journal: The Journal for ImmunoTherapy of Cancer

Authors: Takahiro Nakashima, Tsunenori Ouchida, Yuichi Ishikawa, Yusuke Ito, Taeko Hayakawa, Toshiaki Yoshikawa, Haosong Zhang, Hitomi Kasuya, Yang Li, Tetsuya Matsukawa, Satoshi Inoue, Shinsuke Iida, Hitoshi Kiyoi, Yuki Kagoya

Read the full article.

Hung Trinh

More posts featuring Hung Trinh on OncoDaily.

AML cancer CAR T-cell therapy Haosong Zhang Hitomi Kasuya Hitoshi Kiyoi Hung Trinh OncoDaily Oncology Satoshi Inoue Seneca Therapeutics Shinsuke Iida solid tumors Taeko Hayakawa Takahiro Nakashima Tetsuya Matsukawa TNF-NTF Toshiaki Yoshikawa Tsunenori Ouchida Yang Li Yuichi Ishikawa Yuki Kagoya Yusuke Ito

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