ArticleAmerican journal of cancer research2019
Akt inhibition at the initial stage of CAR-T preparation enhances the CAR-positive expression rate, memory phenotype and in vivo efficacy.
Article in American journal of cancer research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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Who cites it
34 citing papers in PubMed, 43 citations in OpenAlex.
- Enhancing persistence while managing cytokine release syndrome to embrace next-generation CAR-T cell therapy.Journal of translational medicine · 2026Review
- Therapeutic targeting of BCL-2 during CART cell production augments potency through non-apoptotic adaptive changes.Signal transduction and targeted therapy · 2026Article
- Adaptive-like CAR-iPSC-CD4⁺ T cells outperform CD8⁺ counterparts in sustained ALL control.Inflammation and regeneration · 2026Article
- Novel strategies to manage CAR-T cell toxicity.Nature reviews. Drug discovery · 2025Review
- Differential regulation of calcium-NFAT signaling pathway by Akt isoforms: unraveling effector dynamics and exhaustion of cytotoxic T lymphocytes in tumor microenvironment.Journal for immunotherapy of cancer · 2025Article
- Capivasertib enhances chimeric antigen receptor T cell activity in preclinical models of B cell lymphoma.Molecular therapy. Methods & clinical development · 2025Article
- Charged substrate treatment enhances T cell mediated cancer immunotherapy.Nature communications · 2025Article
- Metabolic reprogramming of CAR T cells: a new frontier in cancer immunotherapy.Frontiers in immunology · 2025Review
- Multiomic profiling of chronically activated CD4+ T cells identifies drivers of exhaustion and metabolic reprogramming.PLoS biology · 2024Article
- Reshaping the tumor immune microenvironment to improve CAR-T cell-based cancer immunotherapy.Molecular cancer · 2024Review
- Fueling CARs: metabolic strategies to enhance CAR T-cell therapy.Experimental hematology & oncology · 2024Review
- CAR-T cell manufacturing landscape-Lessons from the past decade and considerations for early clinical development.Molecular therapy. Methods & clinical development · 2024Review
- Tumor-Associated Monocytes Reprogram CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Unlocking the potential of T-cell metabolism reprogramming: Advancing single-cell approaches for precision immunotherapy in tumour immunity.Clinical and translational medicine · 2024Review
- GD2-targeting therapy: a comparative analysis of approaches and promising directions.Frontiers in immunology · 2024Review
- AKT inhibition generates potent polyfunctional clinical grade AUTO1 CAR T-cells, enhancing function and survival.Journal for immunotherapy of cancer · 2023Article
- Crosstalk between autophagy and metabolic regulation of (CAR) T cells: therapeutic implications.Frontiers in immunology · 2023Review
- PGE2-EP2/EP4 signaling elicits mesoCAR T cell immunosuppression in pancreatic cancer.Frontiers in immunology · 2023Article
- Targeting of chimeric antigen receptor T cell metabolism to improve therapeutic outcomes.Frontiers in immunology · 2023Review
- The magic of small-molecule drugs duringFrontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The adoptive transfer of chimeric antigen receptor-modified T (CAR-T) cells is a novel cancer treatment that has led to encouraging breakthroughs in the treatment of haematological malignancies. The efficacy of infused CAR-T cells is associated with a high CAR-positive expression rate, a strong proliferative response and the persistence of CAR-T cells in vivo. Manufacturing CAR-T cells is a process usually associated with the decreased CAR-positive expression rate and terminal differentiation of the infused CAR-T cells, which causes decreased proliferation and persistence of CAR-T cells in vivo. Therefore, the preparation of a high CAR-positive expression rate and few differentiated CAR-T cells is particularly important for clinical cancer treatment. In this study, we transduced and expanded CAR-T cells targeting the epithelial cell adhesion molecule (EpCAM) in the presence of an Akt inhibitor (MK2206) during the initial stage of CAR-T cell preparation. We show that the Akt inhibitor did not suppress the proliferation or effector function of the EpCAM-CAR-T cells but increased the CAR-positive expression rate and decreased the number of terminally differentiated EpCAM-CAR-T cells. Furthermore, EpCAM-CAR-T cells prepared using this protocol appeared to have enhanced antitumor activity in vivo. Taken together, these findings suggest that Akt inhibition during the initial stage of CAR-T cell preparation could improve the performance of CAR-T cells.
Indexed as
Identifiers
31815041PMC6895454W2998305599What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.