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The in vitro generation of multi-tumor antigen-specific cytotoxic T cell clones: Candidates for leukemia adoptive immunotherapy following allogeneic stem cell transplantation
- Source :
- Molecular immunology. 77
- Publication Year :
- 2016
-
Abstract
- Adoptive T-cell immunotherapy is a promising approach to manage and maintain relapse-free survival of leukemia patients, especially following allogeneic stem cell transplantation. Post-transplant adoptive immunotherapy using cytotoxic T lymphocytes (CTLs) of the donor origin provide graft-versus-tumor effects, with or without graft-versus-host disease. Myeloid leukemias express immunogenic leukemia associated antigens (LAAs); such as WT-1, PRAME, MAGE, h-TERT and others, most of them are able to induce specific T cell responses whenever associated with the proper co-stimulation. We investigated the ability of a LAA-expressing hybridoma cell line to induce CTL clones in PBMCs of HLA-matched healthy donors in vitro. The CTL clones were induced by repetitive co-culture with LAAs-expressing, HLA-A*0201(+) hybrid cell line, generated by fusion of leukemia blasts to human immortalized APC (EBV-sensitized B-lymphoblastoid cell line; HMy2). The induced cytotoxic T cell clones were phenotypically and functionally characterized by pentamer analysis, IFN-γ release ELISPOT and cellular cytotoxicity assays. All T cell lines showed robust peptide recognition and functional activity when sensitized with HLA-A*0201-restricted WT-1235-243, hTERT615-624 or PRAME100-108 peptides-pulsed T2 cells, in addition to partially HLA-matched leukemia blasts. This study demonstrates the feasibility of developing multi-tumor antigen-specific T cell lines in allogeneic PBMCs in vitro, using LAA-expressing tumor/HMy2 hybrid cell line model, for potential use in leukemia adoptive immunotherapy in partially matched donor-recipient setting.
- Subjects :
- Enzyme-Linked Immunospot Assay
medicine.medical_treatment
T cell
Immunology
Hematopoietic stem cell transplantation
Biology
Hybrid Cells
In Vitro Techniques
Immunotherapy, Adoptive
Polymerase Chain Reaction
03 medical and health sciences
0302 clinical medicine
Antigens, Neoplasm
medicine
Tumor Cells, Cultured
Cytotoxic T cell
Humans
Molecular Biology
Leukemia
Hematopoietic Stem Cell Transplantation
Immunotherapy
medicine.disease
Combined Modality Therapy
Tumor antigen
Coculture Techniques
CTL
medicine.anatomical_structure
030220 oncology & carcinogenesis
Stem cell
030215 immunology
T-Lymphocytes, Cytotoxic
Subjects
Details
- ISSN :
- 18729142
- Volume :
- 77
- Database :
- OpenAIRE
- Journal :
- Molecular immunology
- Accession number :
- edsair.doi.dedup.....a55109f4ea1fc21a3ce92dbe019f3d07