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Selective refueling of CAR T cells using ADA1 and CD26 boosts antitumor immunity.
Hu, Yue; Sarkar, Abhijit; Song, Kevin; Michael, Sara; Hook, Magnus; Wang, Ruoning; Heczey, Andras; Song, Xiaotong.
Afiliação
  • Hu Y; Department of Translational Medical Sciences, School of Medicine, Texas A&M University, Houston, TX, USA; Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M University, Houston, TX, USA.
  • Sarkar A; Department of Translational Medical Sciences, School of Medicine, Texas A&M University, Houston, TX, USA; Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M University, Houston, TX, USA.
  • Song K; Department of Translational Medical Sciences, School of Medicine, Texas A&M University, Houston, TX, USA; Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M University, Houston, TX, USA; Department of Biology, University of Houston, Houston, T
  • Michael S; Department of Translational Medical Sciences, School of Medicine, Texas A&M University, Houston, TX, USA; Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M University, Houston, TX, USA; Department of Synthesis Biology, University of Houston,
  • Hook M; Department of Translational Medical Sciences, School of Medicine, Texas A&M University, Houston, TX, USA; Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M University, Houston, TX, USA.
  • Wang R; Center for Childhood Cancer Research, Hematology/Oncology & BMT, Abigail Wexner Research Institute at Nationwide Children's Hospital, Department of Pediatrics at The Ohio State University, Columbus, OH, USA.
  • Heczey A; Texas Children's Hospital, Houston, TX, USA; Department of Pediatric, Baylor College of Medicine, Houston, TX, USA.
  • Song X; Department of Translational Medical Sciences, School of Medicine, Texas A&M University, Houston, TX, USA; Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M University, Houston, TX, USA. Electronic address: xsong@tamu.edu.
Cell Rep Med ; 5(5): 101530, 2024 May 21.
Article em En | MEDLINE | ID: mdl-38688275
ABSTRACT
Chimeric antigen receptor (CAR) T cell therapy is hindered in solid tumor treatment due to the immunosuppressive tumor microenvironment and suboptimal T cell persistence. Current strategies do not address nutrient competition in the microenvironment. Hence, we present a metabolic refueling approach using inosine as an alternative fuel. CARcells were engineered to express membrane-bound CD26 and cytoplasmic adenosine deaminase 1 (ADA1), converting adenosine to inosine. Autocrine secretion of ADA1 upon CD3/CD26 stimulation activates CARcells, improving migration and resistance to transforming growth factor ß1 suppression. Fusion of ADA1 with anti-CD3 scFv further boosts inosine production and minimizes tumor cell feeding. In mouse models of hepatocellular carcinoma and non-small cell lung cancer, metabolically refueled CARcells exhibit superior tumor reduction compared to unmodified CARcells. Overall, our study highlights the potential of selective inosine refueling to enhance CAR T therapy efficacy against solid tumors.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Adenosina Desaminase / Imunoterapia Adotiva / Dipeptidil Peptidase 4 / Receptores de Antígenos Quiméricos Limite: Animals / Humans Idioma: En Revista: Cell Rep Med Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Adenosina Desaminase / Imunoterapia Adotiva / Dipeptidil Peptidase 4 / Receptores de Antígenos Quiméricos Limite: Animals / Humans Idioma: En Revista: Cell Rep Med Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos