Abstract
MANY murine and human tumour cells express cell surface antigens cross-reactive with histocompatibility antigens that are expressed on normal cells of unrelated individuals of the species1–7. One approach for generating cytotoxic lymphocytes capable of lysing autologous or syngeneic tumour cells therefore might be to sensitise to the appropriate cross-reactive alloantigen(s). Results obtained in our laboratory indicate that lymphocytes sensitised in mixed leukocyte culture to a pool of normal cells from 20 unrelated individuals8 lyse virtually all allogeneic target cells9, suggesting that the ‘pool’ presents essentially all the target determinants for cytotoxic T lymphocytes (CTL) expressed on normal human cells. We therefore hypothesised that sensitisation of T cells to the ‘pool’ may be a means for generating CTL capable of lysing autologous morphologically transformed cells without the need to experimentally define which alloantigen specificities are expressed on particular transformed cells10. One model in which we have recently demonstrated the efficacy of pool sensitisation involves Epstein–Barr virus transformed human lymphoblastoid cell lines (LCL); normal T lymphocytes sensitised in vitro against the pool lyse autologous 51Cr-labelled LCL cells but not autologous normal T cells, B cells or mitogen-induced blast cells11. Studies were thus undertaken to determine whether leukaemia cells, which are incapable of stimulating cytotoxic responses in autologous lymphocytes12–14, would be lysed by T cells from patients sensitised in vitro with pooled allogeneic cells. We report here that ‘pool’ sensitisation of T cells from patients with hairy cell leukaemia (leukaemic reticuloendotheliosis) gives rise to CTL that lyse autologous leukaemia cells but not autologous normal lymphocytes.
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ZARLING, J., ROBINS, H., RAICH, P. et al. Generation of cytotoxic T lymphocytes to autologous human leukaemia cells by sensitisation to pooled allogeneic normal cells. Nature 274, 269–271 (1978). https://doi.org/10.1038/274269a0
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DOI: https://doi.org/10.1038/274269a0
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