Human antigen-presenting cell/tumour cell hybrids stimulate strong allogeneic responses and present tumour-associated antigens to cytotoxic T cells in vitro.
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.
Dunnion
D J
DJ
Department of Microbiology, Leicester University, UK.
Cywinski
A L
AL
Tucker
V C
VC
Murray
A K
AK
Rickinson
A B
AB
Coulie
P
P
Browning
M J
MJ
D048868:Adaptor Proteins, Signal Transducing; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000276:immunology; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics; D003598:Cytoskeletal Proteins; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D006680:HLA Antigens / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D006825:Hybridomas / Q000276:immunology* / Q000821:virology; D007167:Immunotherapy / Q000379:methods*; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology; D016176:T-Lymphocyte Subsets; D014407:Tumor Cells, Cultured / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D006680:HLA Antigens; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D008562:Membrane Glycoproteins; C484380:PDLIM7 protein, human