'Off-the-Shelf' Immunotherapy: Manufacture of CD8 + T Cells Derived from Hematopoietic Stem Cells

Cellular immunotherapy is revolutionizing cancer treatment. However, autologous transplants are complex, costly, and limited by the number and quality of T cells that can be isolated from and expanded for re-infusion into each patient. This paper demonstrates a stromal support cell-free in vitro met...

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Bibliographic Details
Published in:Cells (Basel, Switzerland) Switzerland), 2021-10, Vol.10 (10), p.2631
Main Authors: Boyd, Nicholas, Cartledge, Kellie, Cao, Huimin, Evtimov, Vera, Pupovac, Aleta, Trounson, Alan, Boyd, Richard
Format: Article
Language:English
Subjects:
Animals
Autografts
Cancer immunotherapy
Cancer therapies
Cattle
CD28 antigen
CD3 antigen
CD8 antigen
CD8+ T cells
CD8-Positive T-Lymphocytes - immunology
Cell culture
Cell Differentiation
Cell Line, Tumor
Cell Proliferation
Chemotherapy
Chimeric antigen receptors
Cord blood
Cytokines
Cytotoxicity
Cytotoxicity, Immunologic
differentiation
Fetal Blood - cytology
Flow cytometry
Hematopoietic stem cells
Hematopoietic Stem Cells - immunology
HSC
Humans
Immune system
Immunotherapy
Lymphocytes
Lymphocytes T
Manufacturers
off-the-shelf immunotherapy
Ovarian cancer
Phenotype
Regulatory approval
Stem cells
T cell receptors
Transplantation
Transplants & implants
Umbilical cord
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Summary:Cellular immunotherapy is revolutionizing cancer treatment. However, autologous transplants are complex, costly, and limited by the number and quality of T cells that can be isolated from and expanded for re-infusion into each patient. This paper demonstrates a stromal support cell-free in vitro method for the differentiation of T cells from umbilical cord blood hematopoietic stem cells (HSCs). For each single HSC cell input, approximately 5 × 10 T cells were created with an initial five days of HSC expansion and subsequent T cell differentiation over 49 days. When the induced in vitro differentiated T cells were activated by cytokines and anti-CD3/CD28 beads, CD8 T cell receptor (TCR) γδ T cells were preferentially generated and elicited cytotoxic function against ovarian cancer cells in vitro. This process of inducing de novo functional T cells offers a possible strategy to increase T cell yields, simplify manufacturing, and reduce costs with application potential for conversion into chimeric antigen receptor (CAR)-T cells for cancer immunotherapy and for allogeneic transplantation to restore immune competence.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells10102631