Cancer vaccine by fusions of dendritic and cancer cells

Abstract

Dendritic cells (DCs) are potent antigen-presenting cells and play a central role in the initiation and regulation of primary immune responses. Therefore, their use for the active immunotherapy against cancers has been studied with considerable interest. The fusion of DCs with whole tumor cells represents in many ways an ideal approach to deliver, process, and subsequently present a broad array of tumor-associated antigens, including those yet to be unidentified, in the context of DCs-derived costimulatory molecules. DCs/tumor fusion vaccine stimulates potent antitumor immunity in the animal tumor models. In the human studies, T cells stimulated by DC/tumor fusion cells are effective in lysis of tumor cells that are used as the fusion partner. In the clinical trials, clinical and immunological responses were observed in patients with advanced stage of malignant tumors after being vaccinated with DC/tumor fusion cells, although the antitumor effect is not as vigorous as in the animal tumor models. This review summarizes recent advances in concepts and techniques that are providing new impulses to DCs/tumor fusions-based cancer vaccination.

Figure 1

Fusions of autologous DCs and autologous tumor cells. The DCs/tumor fusion cells express MHC class I and class II and costimulatory molecules as well as tumor-associated antigens. The fusions are able to process tumor-derived peptides and MHC class I peptides derived from DCs. They form MHC class I-peptide complexes, in the endoplasmic reticulum, which are transported to the surface and presented to CD8+ T cells. Similarly, the fusion cells can also synthesize MHC class II peptides derived from DCs in the endoplasmic reticulum, which are transported to the cytoplasm where MHC class II-peptide complexes are assembled with tumor-derived peptides. These complexes are presented to CD4+ T cells, which are important for efficient CTL induction.

Figure 2

Fusions of autologous DCs and allogeneic tumor cells (DCs/allo-tumor). The DCs/allo-tumor can stimulate both CD4+ and CD8+ T cells as same as fusions of autologous DCs and autologous DCs (DCs/auto-tumor). Moreover, the DCs/allo-tumor can also stimulate alloreactive T cells due to the presence of allogeneic HLA class I molecules from allogeneic tumor cells. Autologous MHC molecules present foreign peptide derived from allogeneic tumor cells to T cell selected to recognize self MHC-foreign peptide complexes. In addition, T cell also can recognize an allogeneic MHC molecule whose structure resembles the self MHC-foreign peptide complexes and structure formed by both the allogeneic MHC molecules and the bound peptide.