ArticleCancer immunology, immunotherapy : CII2011
IL-21-treated naive CD45RA+ CD8+ T cells represent a reliable source for producing leukemia-reactive cytotoxic T lymphocytes with high proliferative potential and early differentiation phenotype.
Article in Cancer immunology, immunotherapy : CII, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- TCR-engaging scaffolds selectively expand antigen-specific T-cells with a favorable phenotype for adoptive cell therapy.Journal for immunotherapy of cancer · 2023Article
- The S enantiomer of 2-hydroxyglutarate increases central memory CD8 populations and improves CAR-T therapy outcome.Blood advances · 2020Article
- Antigen-specific CD8+ memory stem T cells generated from human peripheral blood effectively eradicate allogeneic targets in mice.Stem cell research & therapy · 2018Article
- Article
- Expansion of T Cells with Interleukin-21 for Adoptive Immunotherapy of Murine Mammary Carcinoma.International journal of molecular sciences · 2017Article
- Adoptive Immunotherapy For Leukemia With Ex vivo Expanded T Cells.Current drug targets · 2017Review
- A short CD3/CD28 costimulation combined with IL-21 enhance the generation of human memory stem T cells for adoptive immunotherapy.Journal of translational medicine · 2016Article
- Improving Adoptive T Cell Therapy: The Particular Role of T Cell Costimulation, Cytokines, and Post-Transfer Vaccination.Frontiers in immunology · 2016Review
- Generation of memory T cells for adoptive transfer using clinical-grade anti-CD62L magnetic beads.Bone marrow transplantation · 2015Article
- T-cell and natural killer cell therapies for hematologic malignancies after hematopoietic stem cell transplantation: enhancing the graft-versus-leukemia effect.Haematologica · 2015Review
- Addition of interleukin-21 for expansion of T-cells for adoptive immunotherapy of murine melanoma.International journal of molecular sciences · 2015Article
- Human heat shock protein-specific cytotoxic T lymphocytes display potent antitumour immunity in multiple myeloma.British journal of haematology · 2014Article
- Recombinant IL-21 and anti-CD4 antibodies cooperate in syngeneic neuroblastoma immunotherapy and mediate long-lasting immunity.Cancer immunology, immunotherapy : CII · 2014Article
- Depletion of naive T cells using clinical grade magnetic CD45RA beads: a new approach for GVHD prophylaxis.Bone marrow transplantation · 2014Article
- Uncoupling T-cell expansion from effector differentiation in cell-based immunotherapy.Immunological reviews · 2014Review
- A cytokine cocktail directly modulates the phenotype of DC-enriched anti-tumor T cells to convey potent anti-tumor activities in a murine model.Cancer immunology, immunotherapy : CII · 2013Article
- Modulating the differentiation status of ex vivo-cultured anti-tumor T cells using cytokine cocktails.Cancer immunology, immunotherapy : CII · 2013Article
- Paths to stemness: building the ultimate antitumour T cell.Nature reviews. Cancer · 2012Review
- Alloreactive and leukemia-reactive T cells are preferentially derived from naive precursors in healthy donors: implications for immunotherapy with memory T cells.Haematologica · 2011Article
- Sorting through subsets: which T-cell populations mediate highly effective adoptive immunotherapy?Journal of immunotherapy (Hagerstown, Md. : 1997)Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clinical tumor remissions after adoptive T-cell therapy are frequently not durable due to limited survival and homing of transfused tumor-reactive T cells, what can be mainly attributed to the long-term culture necessary for in vitro expansion. Here, we introduce an approach allowing the reliable in vitro generation of leukemia-reactive cytotoxic T lymphocytes (CTLs) from naive CD8+ T cells of healthy donors, leading to high cell numbers within a relatively short culture period. The protocol includes the stimulation of purified CD45RA+ CD8+ T cells with primary acute myeloid leukemia blasts of patient origin in HLA-class I-matched allogeneic mixed lymphocyte-leukemia cultures. The procedure allowed the isolation of a large diversity of HLA-A/-B/-C-restricted leukemia-reactive CTL clones and oligoclonal lines. CTLs showed reactivity to either leukemia blasts exclusively, or to leukemia blasts as well as patient-derived B lymphoblastoid-cell lines (LCLs). In contrast, LCLs of donor origin were not lysed. This reactivity pattern suggested that CTLs recognized leukemia-associated antigens or hematopoietic minor histocompatibility antigens. Consistent with this hypothesis, most CTLs did not react with patient-derived fibroblasts. The efficiency of the protocol could be further increased by addition of interleukin-21 during primary in vitro stimulation. Most importantly, leukemia-reactive CTLs retained the expression of early T-cell differentiation markers CD27, CD28, CD62L and CD127 for several weeks during culture. The effective in vitro expansion of leukemia-reactive CD8+ CTLs from naive CD45RA+ precursors of healthy donors can accelerate the molecular definition of candidate leukemia antigens and might be of potential use for the development of adoptive CTL therapy in leukemia.
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