The antitumor effect of tumor-draining lymph node cells activated by both anti-CD3 monoclonal antibody and activated B cells as costimulatory-signal-providing cells |
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Authors: | Tadao Okamoto Mamoru Harada Yoshihiro Shinomiya Goro Matsuzaki Kikuo Nomoto |
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Institution: | (1) Department of Immunology, Kyushu University, Maidashi 3-1-1, Higashi-ku, 812 Fukuoka, Japan;(2) Department of Virology, Medical Institute of Bioregulation, Kyushu University, 812 Fukuoka, Japan |
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Abstract: | To establish an efficient cell-culture system for adoptive immunotherapy, we attempted to use lipopolysacharide (LPS)-activated B cells (LPS blasts) as costimulatory-signal-providing cells in the in vitro induction of antitumor effector cells. Both normal and tumor-draining lymph node cells were efficiently activated by both anti-CD3 monoclonal antibody (mAb) and LPS blasts, and subsequently expanded by a low dose of interleukin-2 (IL-2; anti-CD3 mAb and LPS blasts/IL-2). The expanded cells were predominantly CD8+ T cells and showed a low level of tumor-specific cytotoxic T lymphocyte (CTL) activity. The adoptive transfer of B16-melanoma-draining lymph node cells expanded by anti-CD3 mAb and LPS blasts/IL-2 showed significant antitumor effect against the established metastases of B16 in combination with intraperitoneal injections of IL-2. This treatment cured all B16-bearing mice. In addition, these mice also showed tumorspecific protective immunity against B16 at the rechallenge. Considering that activated B cells express several kinds of costimulatory molecules, these findings thus indicate an efficacy of costimulation that is derived from activated B cells for the in vitro induction of tumor-specific CTL, in co-operation with anti-CD3 mAb. The culture system presented here may thus be therapeutically useful, providing potent effectors for adoptive immunotherapy against various types of cancer. |
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Keywords: | Adoptive immunotherapy costimulation Activated B cells Anti-CD3 mAb |
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