Autologous tumor-specific cytotoxic T-lymphocytes in a child with neuroblastoma

Abstract

Activation of peripheral blood lymphocytes from a neuroblastoma patient by co-cultivation with autologous neuroblastoma cells in a mixed lymphocyte-tumor cell culture (A-MLTC) resulted in the generation of cytotoxic activity against the autologous neuroblastoma cell line HNB-MS. A-MLTC was set up in the presence of recombinant human interleukin-2 (IL-2). HNB-MS stimulator was treated with recombinant human interferon-γ (IFN-γ) prior to A-MLTC. CTL generated in short-term culture effectively lysed HNE-MS, while they had no effect on an Epstein-Barr virus transformed autologous B-cell line EB-MS. Moreover, CTL lysed 3 different allogeneic neuroblastoma cell lines, but not a rhabdomyosarcoma cell line RBB. Recombinant human tumor necrosis factor-α (TNF-α) and interleukin-4 (IL-4) enhanced and suppressed CTL generation, respectively, when added to the A-MLTC from the beginning of culture. CD3 + CD4 − CD8 + T cells were the major anti-tumor effectors. Furthermore, 111indium-labeled CTL clearly accumulated in metastatic sites. These results indicate that CTL can be used for adoptive immunotherapy in neuroblastoma. neuroblastoma-specifie CTL / IL-2 receptor