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1.
Tissue Antigens ; 68(2): 115-26, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16866881

ABSTRACT

A panel of stable cell hybrids was generated by fusing a range of marrow-derived and solid tumour-derived human cell lines with the B-lymphoblastoid cell lines, HMy2 or KR4, and expression of immunologically relevant accessory and co-stimulatory molecules, and ability to stimulate allogeneic T-cell responses in vitro was investigated. Hybrid cell lines generated from three marrow-derived tumour cells consistently expressed both MHC class I and class II molecules, a range of accessory and T-cell co-stimulatory ligand molecules, including CD80 and CD86, and directly stimulated markedly enhanced T-cell proliferative responses in vitro, as compared with the parent tumour cell lines. The responses were blocked by addition of CTLA4-Ig fusion protein to the cultures, indicating a role of CD28/B7 interaction in induction of T-cell activation. By contrast, hybrid cells derived from three solid tumours only expressed MHC class II when the parent tumour cell line expressed MHC class II and consistently failed to express CD80 or CD86. These hybrid cells also stimulated greater T-cell proliferative responses in vitro than the parent tumour cell lines, although effective co-stimulation depended on the presence of responder non-T cells in the cultures. The expression of co-stimulatory ligand molecules and ability to directly stimulate strong allogeneic T-cell responses correlated with the EBV latency type of the hybrid cells. These data suggest that phenotypic and functional differences in fusion cells of professional antigen- presenting cells and tumour cells arise as a result of the parent tumour cell type.


Subject(s)
Antigen-Presenting Cells/immunology , B-Lymphocytes/immunology , Cell Fusion , Hybrid Cells/immunology , Lymphocyte Activation , T-Lymphocytes/immunology , Antigen-Presenting Cells/cytology , B-Lymphocytes/cytology , B-Lymphocytes/metabolism , B-Lymphocytes/virology , B7-1 Antigen/immunology , B7-2 Antigen/immunology , Bone Marrow Neoplasms/immunology , Cell Line, Tumor , Cell Proliferation , Female , Herpesvirus 4, Human/physiology , Histocompatibility Antigens Class I/analysis , Histocompatibility Antigens Class II/analysis , Humans , Hybrid Cells/cytology , Melanoma/immunology , Uterine Cervical Neoplasms/immunology
2.
Immunology ; 98(4): 541-50, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10594686

ABSTRACT

Most tumours do not stimulate effective antitumour immune responses in vivo. In order to enhance the immunogenicity of human tumour cells, we fused a variety of tumour cell lines with an Epstein-Barr virus transformed B-lymphoblastoid cell line (EBV B-LCL) in vitro, to produce stable hybrid cells. Hybrid cell lines showed a marked increase in their ability to stimulate primary allogeneic T-cell responses in vitro, as compared with the parent tumour cells. The hybrid cells induced proliferation of naive (CD45RA+) as well as memory (CD45RO+) T lymphocytes, and both CD4+ and CD8+ subpopulations of T cells were directly stimulated. The stimulatory hybrids expressed human leucocyte antigen (HLA) class I and II, and a wide range of surface accessory molecules, including the T-cell co-stimulatory ligand molecules CD40, CD80 (B7.1) and CD86 (B7.2), the expression of which was required for optimal stimulation of T-cell responses. Fusion of the EBVB-LCL with a melanoma cell line (518.A2) yielded hybrid cells that expressed the melanoma-associated antigens MAGE-1 and MAGE-3, and presented these antigens to antigen-specific, HLA class I-restricted cytotoxic T-lymphocyte clones with greater efficiency than the parent melanoma cell line. These findings suggest that the generation of human antigen-presenting cell/tumour cell hybrids offers promise as an approach to cancer immunotherapy.


Subject(s)
Antigen-Presenting Cells/immunology , HLA Antigens/immunology , Hybridomas/immunology , Immunotherapy/methods , Tumor Cells, Cultured/immunology , Adaptor Proteins, Signal Transducing , Antigen Presentation , Antigens, CD/immunology , Antigens, Neoplasm/immunology , B7-1 Antigen/immunology , B7-2 Antigen , CD40 Antigens/immunology , Carrier Proteins/analysis , Carrier Proteins/genetics , Cytoskeletal Proteins , Cytotoxicity Tests, Immunologic , Flow Cytometry , Herpesvirus 4, Human/immunology , Humans , Hybridomas/virology , Intracellular Signaling Peptides and Proteins , LIM Domain Proteins , Lymphocyte Activation , Melanoma/immunology , Membrane Glycoproteins/immunology , Skin Neoplasms/immunology , T-Lymphocyte Subsets
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