Potent in Vivo Anti-tumor Activity of Isolated CD62 Llow Lymph Node Cells Sensitized in Vivo With tumor Lysate-pulsed DC-based Vaccines

Background DC are potent APC that can activate both CD4 and CD8 T cells in vitro and in vivo. Although the efficacy of DC-hased cancer vaccines is currently being evaluated in clinical trials, the systemic immune suppression in cancer patients negatively impacts the clinical benefit of this therapeutic approach. Therefore, in this study we tested the feasibility and anti-tumor effect of adoptive immunotherapy using in vitro-activated CD62Llow lymph node cells that were isolated from DC-vaccinated draining lymph nodes （VDLN）. Methods DC were prepared from BM cells and loaded with tumor lysate for inoculating into naive mice. Subsequently, the VDLN were removed and CD62 Llow cells in the VDLN population isolated, expanded in vitro by 5-day culture with IL-2 and immobilized anti-CD3 stimulation, then injected into mice with established pulmonary tumors. Eighteen days after treatment, mice were killed in order to enumeratepulmonary tumor nodes. Results DC phagocytosed the tumor lysate efficiently and induced detectable T-cell responses and significant cell expansion in the draining lymph nodes. After induction of maturation by LPS treatment, DC expressed higher levels of CD40, CD86 and MHC class Ⅱ molecules. When CD62Llow VDLN cells that had been isolated and expanded in vitro were transferred into tumor-bearing mice, as few as 3 ＊ 106 cells were able to cure metastatic pulmonary tumors in vivo. Conclusion DC-hased VDLN T cells are an important source of anti-tumor effector for adoptive immunotherapy. This study provides a novel and an effective protocol using T-cell adoptive immunotherapy for application in cancer patients; therefore, clinical trials based on this protocol may be warranted.

Potent in Vivo Anti-tumor Activity of Isolated CD62 Llow Lymph Node Cells Sensitized in Vivo With tumor Lysate-pulsed DC-based Vaccines