Human antigen‐presenting cell/tumour cell hybrids stimulate strong allogeneic responses and present tumour‐associated antigens to cytotoxic T cells in vitro

Summary 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.