Abstract
Recombinant IL-6 was found to function as a late-acting killer helper factor (KHF) in the differentiation of cytotoxic T lymphocytes (CTL) and to mediate an antitumor effect in our previous study. Tumor cells transfected with IL-6 cDNA using PM 5 Gneo retrovirus vector induced stronger anti-tumor effect even on non-immunogenic murine tumors. CD 4-8+ CTL and CD 4+ T cells played a role in the in vivo anti-tumor effect of the IL-6 gene-transfectant.
We analyzed the in vivo anti-human tumor effect of IL-6 by using the SCID-PBL/hu mice construcuted with human PBL. Injection of CESS human B tumor cells transfected with the IL-6 cDNA into SCID-PBL/hu mice induced significant CD 3+ human CTL. When human lung cancer cells transfected with IL-6 gene were administered into SCID-PBL/hu mice constructed with syngeneic PBL, cytotoxic cells were generated and prolongation of survival was observed. Furthermore, IL-6 transgenic SCID-hu mice constructed with PBL from a lung cancer patient or a gastric cancer patient exhibited cytotoxic activity against syngenic cancer cells even when non-transfected cancer cells were injected. These IL-6 gene-transfected tumor and SCID mice might provide a useful tool for the analysis of therapeutic effect in human cancers.
Recently an anti-human tumor effect by in vivo transfer of IL-6 gene using adenovirus vector into SCID-PBL/hu mice was exhibited. When SCID-PBL/hu mice were injected with CESS human tumor cells and treated with AdexIL-6, CD 3+ CD 8+ human CTL were generated. Prolongation of survival, regression of tumor and inhibition of metastasis were also observed. Human CD 3+ CD 8+ tumor specific CTL were generated in vivo and tumor growth was inhibited in the SCID-PBL/hu mice which were constructed with PBL from patients with gastric cancer or colon cancer, injected with autologous cancer cells, and treated with AdexIL-6 i.p. Thus, the experimental model using SCID-PBL/hu and cytokine genes delivered by an adenovirus vector might provide a new strategy capable of analyzing anti-human tumor effect by cytokine gene therapy without using human body.
