Antitumor reactivity of lymph node cells primed in vivo with dendritic cell-based vaccines

Tumor lysate-pulsed dendritic cells were used to generate nodal effector T cells in the murine MCA 205 tumor model. Dendritic cells were derived from bone marrow and cultured in granulocyte-macrophage colony-stimulating factor/interleukin 4 before pulsation with tumor lysate. Multiple subcutaneous administrations of tumor lysate-pulsed dendritic cells (TP-DCs) resulted in an approximately eightfold hypertrophy of the vaccine draining nodes, with an increased influx of dendritic (CD11c+/CD80+) cells and B (B220+) cells. The vaccine-primed lymph node (VPLN) cells were secondarily activated with anti-CD3/interleukin 2 and exhibited specific interferon-gamma release to tumor antigen. The adoptive transfer of TP-DC VPLN cells resulted in regression of established 3-day pulmonary metastases. The antitumor reactivity of TP-DC VPLN cells was comparable to anti-CD3/interleukin 2 activated tumor-draining lymph node cells. However, the admixture of keyhole limpet hemocyanin (KLH) with tumor lysate during pulsation of dendritic cells significantly enhanced the induction of tumor-reactive VPLN cells. Tumor lysate-pulsed dendritic cells can be used as a strategy to generate effector T cells for adoptive immunotherapy.