ArticleJCI insight2017
Inhibition of AKT signaling uncouples T cell differentiation from expansion for receptor-engineered adoptive immunotherapy.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers.
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Who cites it
144 citing papers in PubMed, 214 citations in OpenAlex.
- Boosting CAR T cell efficacy in cancer with metabolic insights from design to diet.Nature reviews. Cancer · 2026Review
- In Vitro Inhibition of STAT5 Signaling Limits CD8+ T-cell Exhaustion and Improves Outcomes in Adoptive T-cell Therapy.Cancer immunology research · 2026Article
- Decoding immunotherapy resistance in multiple myeloma: genetic insights and approaches to counter resistance.Science China. Life sciences · 2026Review
- Spatiotemporal dynamics of adoptively transferred stem-like CD8bioRxiv : the preprint server for biology · 2026Article
- Therapeutic targeting of BCL-2 during CART cell production augments potency through non-apoptotic adaptive changes.Signal transduction and targeted therapy · 2026Article
- Combining Small-Molecular Compounds With CAR T-Cell Therapy: Novel Strategies for Enhanced Cancer Immunotherapy.Cancer innovation · 2026Review
- T-cell Priming by High-Avidity Neoantigens in Lymph Nodes Augments Adoptive Immunotherapy.Cancer immunology research · 2026Article
- Fine-tuning BACH2 dosage balances stemness and effector function to enhance antitumor T cell therapy.Nature immunology · 2026Article
- CAR-adapted PIK3CD base editing enhances T cell anti-tumor potency.Nature cancer · 2026Article
- 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
- A phase 1 trial of HPV16 E7 T-cell receptor-engineered T cells in patients with relapsed/refractory HPV16-positive cancers (KITE-439 trial).Frontiers in oncology · 2026Article
- Regulation of T cell exhaustion and stemness: molecular mechanisms and implications for cancer immunotherapy.Cellular & molecular immunology · 2026Review
- Developing immunotherapies through glycosylation reprogramming to combat solid cancers.Frontiers in immunology · 2026Review
- Research progress on resistance mechanisms to CAR-T cell therapy in diffuse large B-cell lymphoma.Frontiers in oncology · 2026Review
- Article
- AMPK agonism optimizes the in vivo activation and antileukemic efficacy of chimeric antigen receptor T cells.Journal for immunotherapy of cancer · 2025Article
- FOXO1 phosphorylation as a context-dependent molecular switch in cancer: from mechanisms to precision therapy.World journal of surgical oncology · 2025Review
- Tempered signal strength via low-dose MEK inhibition optimizes therapeutic performance of engineered T cells.Journal for immunotherapy of cancer · 2025Article
- Current status of chimeric antigen receptor T cell therapy and its exhaustion mechanism.Immunotherapy · 2025Review
84 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 1 country.
Funding
Abstract
Adoptive immunotherapies using T cells genetically redirected with a chimeric antigen receptor (CAR) or T cell receptor (TCR) are entering mainstream clinical practice. Despite encouraging results, some patients do not respond to current therapies. In part, this phenomenon has been associated with infusion of reduced numbers of early memory T cells. Herein, we report that AKT signaling inhibition is compatible with CAR and TCR retroviral transduction of human T cells while promoting a CD62L-expressing central memory phenotype. Critically, this intervention did not compromise cell yield. Mechanistically, disruption of AKT signaling preserved MAPK activation and promoted the intranuclear localization of FOXO1, a transcriptional regulator of T cell memory. Consequently, AKT signaling inhibition synchronized the transcriptional profile for FOXO1-dependent target genes across multiple donors. Expression of an AKT-resistant FOXO1 mutant phenocopied the influence of AKT signaling inhibition, while addition of AKT signaling inhibition to T cells expressing mutant FOXO1 failed to further augment the frequency of CD62L-expressing cells. Finally, treatment of established B cell acute lymphoblastic leukemia was superior using anti-CD19 CAR-modified T cells transduced and expanded in the presence of an AKT inhibitor compared with conventionally grown T cells. Thus, inhibition of signaling along the PI3K/AKT axis represents a generalizable strategy to generate large numbers of receptor-modified T cells with an early memory phenotype and superior antitumor efficacy.
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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.