ArticleHuman gene therapy2022
Adenosine Deaminase 1 Overexpression Enhances the Antitumor Efficacy of Chimeric Antigen Receptor-Engineered T Cells.
Article in Human gene therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 43 citations in OpenAlex.
- T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy.Signal transduction and targeted therapy · 2026Review
- Engineering the next generation of cellular therapies for solid tumors: multi-specific armored CARs and TME reprogramming strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- ADA2-Functionalized OMVs Remodel the Tumor Microenvironment in Pancreatic Cancer.Pharmaceutics · 2026Article
- Efficacy analysis of CAR-T cells against CD123-positive malignant tumors and exploration of the feasibility of combination therapy with venetoclax.Annals of hematology · 2026Article
- Review
- Rewiring T Cell Metabolism to Enhance CAR T Cell Function in Solid Tumor Microenvironments.Pharmaceutics · 2025Review
- Fine tuning towards the next generation of engineered T cells.Nature biomedical engineering · 2025Review
- Beta-blockers prolong response to androgen deprivation therapy in prostate cancer through modulation of the neuro-immuno-oncology axis.Journal of translational medicine · 2025Article
- Hypoxic link between cancer cells and the immune system: The role of adenosine and lactate.Oncology research · 2025Review
- Above and beyond senescence and CAR T cell: advances and future perspectives.Frontiers in immunology · 2025Review
- Current strategies for armoring chimeric antigen receptor T-cells to overcome barriers of the solid tumor microenvironment.Frontiers in immunology · 2025Review
- Armoring chimeric antigen receptor (CAR) T cells as micropharmacies for cancer therapy.Immuno-oncology technology · 2024Review
- Tumor Microenvironment Drives the Cross-Talk Between Co-Stimulatory and Inhibitory Molecules in Tumor-Infiltrating Lymphocytes: Implications for Optimizing Immunotherapy Outcomes.International journal of molecular sciences · 2024Review
- Applying metabolic control strategies to engineered T cell cancer therapies.Metabolic engineering · 2024Review
- Deciphering the tumor immune microenvironment from a multidimensional omics perspective: insight into next-generation CAR-T cell immunotherapy and beyond.Molecular cancer · 2024Review
- Apoptosis, a Metabolic "Head-to-Head" between Tumor and T Cells: Implications for Immunotherapy.Cells · 2024Review
- Selective refueling of CAR T cells using ADA1 and CD26 boosts antitumor immunity.Cell reports. Medicine · 2024Article
- Inosine induces stemness features in CAR-T cells and enhances potency.Cancer cell · 2024Article
- Engineering CREB-activated promoters for adenosine-induced gene expression.Biotechnology journal · 2024Article
- Optimized expression and purification of a human adenosine deaminase in E. coli and characterization of its Asp8Asn variant.Protein expression and purification · 2024Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Chimeric antigen receptor (CAR) T cell therapy mediates unprecedented benefit in certain leukemias and lymphomas, but has yet to achieve similar success in combating solid tumors. A substantial body of work indicates that the accumulation of adenosine in the solid tumor microenvironment (TME) plays a crucial role in abrogating immunotherapies. Adenosine deaminase 1 (ADA) catabolizes adenosine into inosine and is indispensable for a functional immune system. We have, for the first time, engineered CAR T cells to overexpress ADA. To potentially improve the pharmacokinetic profile of ADA, we have modified the overexpressed ADA in two ways, through the incorporation of a (1) albumin-binding domain or (2) collagen-binding domain. ADA and modified ADA were successfully expressed by CAR T cells and augmented CAR T cell exhaustion resistance. In a preclinical engineered ovarian carcinoma xenograft model, ADA and collagen-binding ADA overexpression significantly enhanced CAR T cell expansion, tumor tissue infiltration, tumor growth control, and overall survival, whereas albumin-binding ADA overexpression did not. Furthermore, in a syngeneic colon cancer solid tumor model, the overexpression of mouse ADA by cancer cells significantly reduced tumor burden and remodeled the TME to favor antitumor immunity. The overexpression of ADA for enhanced cell therapy is a safe, straightforward, reproducible genetic modification that can be utilized in current CAR T cell constructs to result in an armored CAR T product with superior therapeutic potential.
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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.