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. 1992 Jul;66(1):20–26. doi: 10.1038/bjc.1992.210

Large-scale culture system of human CD4+ helper/killer T cells for the application to adoptive tumour immunotherapy.

Y Nakamura 1, Y Tokuda 1, M Iwasawa 1, H Tsukamoto 1, M Kidokoro 1, N Kobayashi 1, S Kato 1, T Mitomi 1, S Habu 1, T Nishimura 1
PMCID: PMC1977880  PMID: 1353365

Abstract

A simple method for the rapid expansion of human CD4+ T cells with both helper and killer functions was established. CD4+ T cells separated from peripheral blood mononuclear cells using immunomagnetic beads were stimulated with immobilised OKT-3 monoclonal antibody (mAb) plus recombinant interleukin 2 (rIL-2) in 96 well culture plates. After 6 day-culture, the CD4+ T cells were restimulated by immobilised OKT-3 mAb for an additional 24 h, then inoculated into concentrated rotary-tissue culture bag and cultured for further 9 days. This procedure yielded a 3000-fold increase in cell number (about 3-5 x 10(9) per bag). Most of the cells (over 96%) continued to express CD4+ antigen and retained their capacity to produce IL-2. The activated CD4+ T cells showed marked cytotoxicity against Fc receptor positive tumour cells in the presence of OKT-3 mAb. Moreover, we succeeded in a specific targeting of the expanded CD4+ helper/killer T cells to c-erb B-2 positive tumour cells by means of anti-CD3 x anti-c-erb B-2 bispecific antibody. These results suggested that our established simple system will be available for the expansion of large number of CD4+ helper/killer T cells which may provide an efficient strategy for adoptive tumour immunotherapy.

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Selected References

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