Dendritic Cell/Tumor Fusion Vaccine(Beth Israel Deaconess Medical Center)

Vaccination with fusions of dendritic cells (DCs) and mucin-1 (MUC1)-positive tumor cells (FC/MUC1) induces MUC1-specific antitumor immunity. However, little is known about the function of Cluster of Differentiation (CD)4 T-cells primed with FC/MUC1 in MUC1 transgenic (MUC1.Tg) mice.

CD4 T-cells primed with FC/MUC1 were analyzed by flow cytometry. Antitumor immunity by adoptive transfer of primed CD4 T-cells in Rag2(-/-) mice was assessed.

The effector and memory T-cells generated with FC/MUC1 were crucial to maintenance of long-term antitumor immunity. MUC1-8-mer peptide SAPDTRPA presented by FC/MUC1 was recognized by CD4 and CD8 T-cells. A subset of primed CD4 T-cells possessed cytotoxicity to lyse major histocompatibility complex (MHC) class I and MUC1 positive tumor cells. Interestingly, adoptive transfer of primed CD4 T-cells prevented lung metastasis in Rag2(-/-) mice.

CD4 T-cells primed by FC/MUC1 play direct role in antitumor immunity.

Dendritic cell (DC)-based tumor vaccine is a promising therapy for malignancies. Recent studies showed greater potency with DC/tumor fusion vaccines against acute myeloid leukemia and melanoma compared with lysate-pulsed DC vaccines. We compared these two vaccine strategies against murine colon cancer and investigated whether DC/tumor fusion cells continue to produce tumor antigens following fusion as a possible explanation for their increased potency. Using a mouse colon cancer model, CT26, we first showed that the DC/CT26 fusion vaccine is more effective in preventing tumor implantation than CT26 lysate-pulsed DC vaccine. Next, CT26 made to constitutively produce bioactive TGF-beta, a surrogate of tumor-derived products, was fused to DCs and found to produce bioactive TGF-beta 72 h after fusion. Our results suggest the DC/tumor fusion vaccine is more potent against colon cancer than the lysate-pulsed DC vaccine. These fusion cells have the distinct advantage of prolonged interaction with tumor antigens in vivo.