Dataset Information

Adoptive Immunotherapy: A Human Pluripotent Stem Cell Perspective.

ABSTRACT: The past decade has witnessed significant advances in cancer immunotherapy, particularly through the adoptive transfer of engineered T cells in treating advanced leukemias and lymphomas. Despite these excitements, challenges remain with scale, cost, and ensuring quality control of engineered immune cells, including chimeric antigen receptor T, natural killer cells, and macrophages. The advent of human pluripotent stem cells (hPSCs), including human embryonic stem cells and induced pluripotent stem cells, has transformed immunotherapy by providing a scalable, off-the-shelf source of any desired immune cells for basic research, translational studies, and clinical interventions. The tractability of hPSCs for gene editing could also generate homogenous, universal cellular products with custom functionality for individual or combinatory therapeutic applications. This review will explore various immune cell types whose directed differentiation from hPSCs has been achieved and recently adapted for translational immunotherapy and feature forward-looking bioengineering techniques shaping the future of the stem cell field.

SUBMITTER: Jin G

PROVIDER: S-EPMC10318121 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Adoptive Immunotherapy: A Human Pluripotent Stem Cell Perspective.

Jin Gyuhyung G Chang Yun Y Harris Jackson Duke JD Bao Xiaoping X

Cells, tissues, organs 20230104 5

The past decade has witnessed significant advances in cancer immunotherapy, particularly through the adoptive transfer of engineered T cells in treating advanced leukemias and lymphomas. Despite these excitements, challenges remain with scale, cost, and ensuring quality control of engineered immune cells, including chimeric antigen receptor T, natural killer cells, and macrophages. The advent of human pluripotent stem cells (hPSCs), including human embryonic stem cells and induced pluripotent st ...[more]

PMID: 36599319

Similar Datasets

Project description:Background: Chimeric antigen receptor (CAR) T cell treatment involves in vitro production of T cells from patient blood with synthetic receptors specific to a cancer antigen. They circumvent the major histocompatibility complex to recognize the tumor antigen, reducing hematologic malignancy remission rates by 80%. Considering the efficacy of CAR-T treatment, the present work aimed at generating functional clusters of differentiation (CD)8 + T cells from human induced pluripotent stem cells (hiPSC) and to generate hiPS-CAR-T cells with high antigen-specific cytotoxicity. Methods: The Alkaline phosphatase assay and MycoEasy rapid mycoplasma detection kit was implemented for detection of hiPSCs and mycoplasma, respectively. The CD34+ HSPCs were harvested in AggreWellTM 400 using a 37-micron reversible strainer. Likewise, the lymphoid progenitor and CD4+CD8+ DP T cells were also harvested. The Cell Counting Kit-8 (CCK-8) assay was used to mark cytotoxicity and ELISA was used to detect IFN-γ secretion. Further, flow cytometry and transwell chambers were used to assess cell cycle, and migration and invasion. Finally, the in vivo antitumor effects of the CAR-T cells were evaluated using experimental animals (mice). Results: Results revealed that a serum-free, feeder layer-free differentiation system significantly yielded hiPSC-based T cell immunotherapy with interleukin-2, interleukin-15, and activators at the differentiation stage to promote the maturation of these cells into human induced pluripotent stem (hiPS)-T cells. The infection of hiPSCs with the CD19 CAR lentivirus resulted in the production of the hiPSC-CAR-T cells. We validated the function of hiPS-CAR-T cells in vivo and in vitro experimentation which revealed no significant differences in cell morphology and function between hiPSC-derived hiPS-CAR-T cells and peripheral blood-derived CAR-T cells. Conclusion: This study developed a culture method that is efficient and clinically useful to make functional CD8+ T cells from hiPSC and to get hiPS-CAR-T cells with high antigen-specific cytotoxicity that are not very different from CAR T cells found in peripheral blood. As a result, our findings may open the way for the clinical use of hiPSC to create functional CD8+ T and hiPS-CAR-T cells cells for use in cell-based cancer therapy.

Dataset Information

Adoptive Immunotherapy: A Human Pluripotent Stem Cell Perspective.

Publications

Adoptive Immunotherapy: A Human Pluripotent Stem Cell Perspective.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets