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Published in: Molecular Cancer 1/2024

Open Access 01-12-2024 | Solid Tumor | Correspondence

Unveiling a novel fusion gene enhances CAR T cell therapy for solid tumors

Authors: Zefeng Zhou, Yongming Xia, Ruixiu Chen, Panpan Gao, Shiwei Duan

Published in: Molecular Cancer | Issue 1/2024

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Abstract

The efficacy of Adoptive Cell Transfer Therapy (ACT) in combating hematological tumors has been well-documented, yet its application to solid tumors faces formidable hurdles, chief among them being the suboptimal therapeutic response and the immunosuppressive milieu within the tumor microenvironment (TME). Recently, Garcia, J. et al. present compelling findings shedding light on potential breakthroughs in this domain. Their investigation reveals the pronounced augmentation of anti-tumor activity in CAR T cells through the introduction of a T cell neoplasm fusion gene, CARD11-PIK3R3. The incorporation of this gene into engineered T cell therapy holds promise as a formidable tool in the arsenal of cancer immunotherapy. The innovative strategy outlined not only mitigates the requirement for high doses of CAR T cells but also enhances tumor control while exhibiting encouraging safety profiles. The exploration of the CARD11-PIK3R3 fusion gene represents an advancement in our approach to bolstering the anti-tumor efficacy of immunotherapeutic interventions. Nonetheless, the imperative for further inquiry to ascertain its transfection efficiency and long-term safety cannot be overstated. Nevertheless, this seminal investigation offers a beacon of hope in surmounting the formidable treatment impediments posed by solid tumors, paving the way for a transformative era in cancer therapeutics.
Literature
1.
2.
go back to reference Miller BC, Sen DR, Al Abosy R, Bi K, Virkud YV, LaFleur MW, et al. Subsets of exhausted CD8(+) T cells differentially mediate tumor control and respond to checkpoint blockade. Nat Immunol. 2019;20(3):326–36.CrossRefPubMedPubMedCentral Miller BC, Sen DR, Al Abosy R, Bi K, Virkud YV, LaFleur MW, et al. Subsets of exhausted CD8(+) T cells differentially mediate tumor control and respond to checkpoint blockade. Nat Immunol. 2019;20(3):326–36.CrossRefPubMedPubMedCentral
3.
go back to reference Kim HD, Park S, Jeong S, Lee YJ, Lee H, Kim CG, et al. 4-1BB delineates distinct activation status of exhausted tumor-infiltrating CD8(+) T cells in Hepatocellular Carcinoma. Hepatology. 2020;71(3):955–71.CrossRefPubMed Kim HD, Park S, Jeong S, Lee YJ, Lee H, Kim CG, et al. 4-1BB delineates distinct activation status of exhausted tumor-infiltrating CD8(+) T cells in Hepatocellular Carcinoma. Hepatology. 2020;71(3):955–71.CrossRefPubMed
4.
go back to reference Li X, Li Y, Dong L, Chang Y, Zhang X, Wang C et al. Decitabine priming increases anti-PD-1 antitumor efficacy by promoting CD8 + progenitor exhausted T cell expansion in tumor models. J Clin Invest. 2023;133(7). Li X, Li Y, Dong L, Chang Y, Zhang X, Wang C et al. Decitabine priming increases anti-PD-1 antitumor efficacy by promoting CD8 + progenitor exhausted T cell expansion in tumor models. J Clin Invest. 2023;133(7).
5.
go back to reference Scharping NE, Rivadeneira DB, Menk AV, Vignali PDA, Ford BR, Rittenhouse NL, et al. Mitochondrial stress induced by continuous stimulation under hypoxia rapidly drives T cell exhaustion. Nat Immunol. 2021;22(2):205–15.CrossRefPubMedPubMedCentral Scharping NE, Rivadeneira DB, Menk AV, Vignali PDA, Ford BR, Rittenhouse NL, et al. Mitochondrial stress induced by continuous stimulation under hypoxia rapidly drives T cell exhaustion. Nat Immunol. 2021;22(2):205–15.CrossRefPubMedPubMedCentral
6.
go back to reference Codarri Deak L, Nicolini V, Hashimoto M, Karagianni M, Schwalie PC, Lauener L, et al. PD-1-cis IL-2R agonism yields better effectors from stem-like CD8(+) T cells. Nature. 2022;610(7930):161–72.CrossRefPubMedPubMedCentral Codarri Deak L, Nicolini V, Hashimoto M, Karagianni M, Schwalie PC, Lauener L, et al. PD-1-cis IL-2R agonism yields better effectors from stem-like CD8(+) T cells. Nature. 2022;610(7930):161–72.CrossRefPubMedPubMedCentral
7.
go back to reference Garcia J, Daniels J, Lee Y, Zhu I, Cheng K, Liu Q, et al. Naturally occurring T cell mutations enhance engineered T cell therapies. Nature. 2024;626(7999):626–34.CrossRefPubMed Garcia J, Daniels J, Lee Y, Zhu I, Cheng K, Liu Q, et al. Naturally occurring T cell mutations enhance engineered T cell therapies. Nature. 2024;626(7999):626–34.CrossRefPubMed
Metadata
Title
Unveiling a novel fusion gene enhances CAR T cell therapy for solid tumors
Authors
Zefeng Zhou
Yongming Xia
Ruixiu Chen
Panpan Gao
Shiwei Duan
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2024
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-024-02007-w

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