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.
Tanigawa
K
K
Division of Surgical Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor 48109-0932, USA.
Takeshita
N
N
Eickhoff
G A
GA
Shimizu
K
K
Chang
A E
AE
D000276:Adjuvants, Immunologic; D019264:Adoptive Transfer; D000818:Animals; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology / Q000628:therapy*; D006241:Haptens / Q000494:pharmacology; D006433:Hemocyanins / Q000494:pharmacology; D016130:Immunophenotyping; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D006241:Haptens; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin