Long-lived fusions of human haematological tumour cells and B-lymphoblastoid cells induce tumour antigen-specific cytotoxic T-cell responses in vitro.
Tumour-specific cytotoxic T-cells (CTL) are important anti-cancer immune effectors. Most tumour cells, however, do not stimulate effective anti-tumour immune responses, in vivo or in vitro. To enhance tumour cell immunogenicity, we fused human tumour cells from haematological malignancies with the B-lymphoblastoid cell line (LCL), HMy2, to generate a panel of long-lived, self replicating LCL/tumour hybrid cell lines. The LCL/tumour hybrid cell lines expressed HLA class I and class II molecules, CD80 and CD86, and a range of known tumour associated antigens (TAAs). In vitro stimulation of PBLs from healthy, HLA-A2+ individuals by hybrid cell lines induced tumour antigen-specific CTLs to TAAs, including survivin, MAGE-A1, NY-ESO-1 and WT-1. Individual hybrid cell lines simultaneously induced CTL to multiple TAAs. In vitro stimulation of PBL from 2 patients with acute myeloid leukaemia by autologous LCL/tumour hybrid cell lines induced CTL capable of killing the patient's own tumour cells. Our data show, for the first time, that hybrid cell lines formed by fusion of HMy2 cells and haematological tumour cells induce tumour- and tumour antigen-specific cytotoxic T-cell responses in vitro. Hybrid cell lines such as those described may represent novel reagents for use in the immunotherapy of haematological malignancies.
Department of Infection, Immunity & Inflammation, University of Leicester, Leicester, UK.
Yehia S
YS
Mohamed
Debbie
D
Dunnion
Iryna
I
Teobald
Renata
R
Walewska
Michael J
MJ
Browning
D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology; D051940:B7-2 Antigen / Q000235:genetics / Q000276:immunology; D002459:Cell Fusion; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D015870:Gene Expression / Q000276:immunology; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology; D019337:Hematologic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D006801:Humans; D006822:Hybrid Cells / Q000276:immunology*; D007167:Immunotherapy; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology; D009360:Neoplastic Cells, Circulating; D000077022:Survivin; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C107489:BIRC5 protein, human; D015789:HLA-A2 Antigen; D000949:Histocompatibility Antigens Class II; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D000077022:Survivin