ArticleJournal for immunotherapy of cancer2023
AKT inhibition generates potent polyfunctional clinical grade AUTO1 CAR T-cells, enhancing function and survival.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026Review
- Challenges and advances in CAR-T cell therapy for B-ALL.Biomarker research · 2026Review
- Therapeutic targeting of BCL-2 during CART cell production augments potency through non-apoptotic adaptive changes.Signal transduction and targeted therapy · 2026Article
- CAR-T cell therapies are coming after glioblastoma: An overview of early phase clinical trials and future perspectives.iScience · 2026Review
- AI-guided CAR designs and targeted pathway modulation to enhance multi-antigen CAR T cell durability and overcome antigen escape.Nature communications · 2026Article
- Adaptive-like CAR-iPSC-CD4⁺ T cells outperform CD8⁺ counterparts in sustained ALL control.Inflammation and regeneration · 2026Article
- Beneficial effect of resveratrol on T cell oxidative metabolism and anti-tumor function is conditioned by priorMolecular therapy. Methods & clinical development · 2025Article
- Capivasertib enhances chimeric antigen receptor T cell activity in preclinical models of B cell lymphoma.Molecular therapy. Methods & clinical development · 2025Article
- Dual-targeting CAR T cells for B-cell acute lymphoblastic leukemia and B-cell non-Hodgkin lymphoma.Blood advances · 2025Review
- TIL Therapy in Lung Cancer: Current Progress and Perspectives.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Reshaping the tumor immune microenvironment to improve CAR-T cell-based cancer immunotherapy.Molecular cancer · 2024Review
- CAR-T cell manufacturing landscape-Lessons from the past decade and considerations for early clinical development.Molecular therapy. Methods & clinical development · 2024Review
- PSCA-CAR T cell therapy in metastatic castration-resistant prostate cancer: a phase 1 trial.Nature medicine · 2024Article
- Article
- Fc receptor-like 5 (FCRL5)-directed CAR-T cells exhibit antitumor activity against multiple myeloma.Signal transduction and targeted therapy · 2024Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
backgroundAUTO1 is a fast off-rate CD19-targeting chimeric antigen receptor (CAR), which has been successfully tested in adult lymphoblastic leukemia. Tscm/Tcm-enriched CAR-T populations confer the best expansion and persistence, but Tscm/Tcm numbers are poor in heavily pretreated adult patients. To improve this, we evaluate the use of AKT inhibitor (VIII) with the aim of uncoupling T-cell expansion from differentiation, to enrich Tscm/Tcm subsets.
methodsVIII was incorporated into the AUTO1 manufacturing process based on the semiautomated the CliniMACS Prodigy platform at both small and cGMP scale.
resultsAUTO1 manufactured with VIII showed Tscm/Tcm enrichment, improved expansion and cytotoxicity in vitro and superior antitumor activity in vivo. Further, VIII induced AUTO1 Th1/Th17 skewing, increased polyfunctionality, and conferred a unique metabolic profile and a novel signature for autophagy to support enhanced expansion and cytotoxicity. We show that VIII-cultured AUTO1 products from B-ALL patients on the ALLCAR19 study possess superior phenotype, metabolism, and function than parallel control products and that VIII-based manufacture is scalable to cGMP.
conclusionUltimately, AUTO1 generated with VIII may begin to overcome the product specific factors contributing to CD19+relapse.
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