Inosine Induces Stemness Features in CAR T cells and Enhances Potency

Klysz, Dorota D.; Fowler, Carley; Malipatlolla, Meena; Stuani, Lucille; Freitas, Katherine A.; Meier, Stefanie; Dániel, Bence; Sandor, Katalin; Xu, Peng; Huang, Jing; Labanieh, Louai; Leruste, Amaury; Bashti, Malek; Keerthi, Vimal; Mata-Alcazar, Janette; Gkitsas, Nikolaos; Guerrero, Justin A.; Fisher, Chris J; Patel, Sunny; Asano, Kyle; Patel, Shabnum; Davis, Kara L.; Satpathy, Ansuman T.; Feldman, Steven A.; Sotillo, Elena; Mackall, Crystal L.

doi:10.1101/2023.04.21.537859

Cited by 3 publications

(2 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…INO supplement could also enhanced CAR-T cells function by inducing metabolic reprogramming, diminishing glycolysis and increasing oxidative phosphorylation during scalable manufacturing of CAR-T cells. [106]…”

Section: Strategies For Improving the Effectiveness Of Car-t Cells By...mentioning

confidence: 99%

Targeting metabolism to improve CAR-T cells therapeutic efficacy

Liu,

Zhao,

Gao

et al. 2024

Chinese Medical Journal

View full text Add to dashboard Cite

Chimeric antigen receptor T (CAR-T) cell therapy achieved advanced progress in the treatment of hematological tumors. However, the application of CAR-T cell therapy for solid tumors still faces many challenges. Competition with tumor cells for metabolic resources in an already nutrient-poor tumor microenvironment is a major contributing cause to CAR-T cell therapy’s low effectiveness. Abnormal metabolic processes are now acknowledged to shape the tumor microenvironment, which is characterized by increased interstitial fluid pressure, low pH level, hypoxia, accumulation of immunosuppressive metabolites, and mitochondrial dysfunction. These factors are important contributors to restriction of T cell proliferation, cytokine release, and suppression of tumor cell-killing ability. This review provides an overview of how different metabolites regulate T cell activity, analyzes the current dilemmas, and proposes key strategies to reestablish the CAR-T cell therapy’s effectiveness through targeting metabolism, with the aim of providing new strategies to surmount the obstacle in the way of solid tumor CAR-T cell treatment.

show abstract

Section: Strategies For Improving the Effectiveness Of Car-t Cells By...mentioning

confidence: 99%

Targeting metabolism to improve CAR-T cells therapeutic efficacy

Liu,

Zhao,

Gao

et al. 2024

Chinese Medical Journal

View full text Add to dashboard Cite

show abstract

“…CAR-T cells stand at the forefront of immunotherapy, holding promise for extending their impact to a broader spectrum of cancers and transforming the landscape of oncological care. It is now also realized that the frequent failure of CAR-T treatment [7,8] may be intrinsically linked with suboptimal differentiation and metabolic rewiring, and recent reports suggest ways to address this [9,10]. The review by Taylor et al underlines the importance of metabolism in the generation, production, and function of those T cells.…”

mentioning

confidence: 99%

Immunometabolism unveiled: Pioneering breakthroughs in cancer therapeutics

Eldering,

Ricci

2024

Molecular Oncology

View full text Add to dashboard Cite

The field of immunometabolism cannot be considered ‘emerging’ anymore; it is at the moment one of the most active and rapidly evolving areas of biomedical research. Its hottest zone is cancer immunometabolism. This is partly due to the clinical application of immunotherapy, with either antibodies (checkpoint blockade) or cellular therapies (e.g., CAR‐T cells). In addition, the proliferating tumor cells create a nutrient‐deprived microenvironment that impairs the metabolic fitness and functionality of infiltrating immune cells such as T cells, NK cells, and macrophages. The key concepts are bidirectional metabolic signaling, plus the conviction that a better understanding of these processes will improve current immunotherapies, and foster new tools and targets for treatment. This collection of reviews will address various exciting aspects from junior and established scientists in the field.

show abstract

Modulation of the ATP-adenosine signaling axis combined with radiotherapy facilitates anti-cancer immunity in brain metastasis

Salamero-Boix,

Schulz,

Anthes

et al. 2024

Preprint

View full text Add to dashboard Cite

The immunosuppressive microenvironment in the brain poses a major limitation to successful therapy for brain metastases. Here we report that blockade of the ATP-to-adenosine-converting enzymes CD39 and CD73 and the adenosine receptor A2AR in combination with radiotherapy attenuates tumor progression in a breast-to-brain metastasis model by facilitating anti-cancer immunity. Immunophenotyping revealed loss of exhausted T cells and higher abundance of anti-cancer effector T cell populations. This effect was accompanied by a decrease of immunosuppressive lipid-laden macrophages and an expansion of CD14CD33high macrophages associated with antigen presentation. Analyses of human brain metastases samples supports a role of the ATP-adenosine signaling axis in modulating tumor inflammation and identified expression of CD39 and adenosine deaminase as predictive markers for patient survival and/or immune infiltration. Our findings demonstrate that the adenosine axis represents a druggable pathway to achieve local immunomodulation and treatment response, opening a new therapeutic avenue for brain metastases patients.

show abstract

Inosine Induces Stemness Features in CAR T cells and Enhances Potency

Cited by 3 publications

References 56 publications

Targeting metabolism to improve CAR-T cells therapeutic efficacy

Targeting metabolism to improve CAR-T cells therapeutic efficacy

Immunometabolism unveiled: Pioneering breakthroughs in cancer therapeutics

Modulation of the ATP-adenosine signaling axis combined with radiotherapy facilitates anti-cancer immunity in brain metastasis

Contact Info

Product

Resources

About