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Cytotherapy. 2016 Apr;18(4):570-80. doi: 10.1016/j.jcyt.2016.01.005.

Dendritic-tumor cell hybrids induce tumor-specific immune responses more effectively than the simple mixture of dendritic and tumor cells.

Author information

1
Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
2
Rebirth Excellence Cluster and Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
3
Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil; Cell and Molecular Therapy Center, NUCEL-NETCEM, University of São Paulo, São Paulo, Brazil. Electronic address: jbarbuto@icb.usp.br.

Abstract

BACKGROUND AIMS:

Dendritic cell (DC)-tumor cell hybrids have been used clinically in cancer immunotherapy, but their advantage over the simple mixture of tumor cells and DCs is still a matter of controversy. In this study, we compared DC-tumor cell hybrids with the non-fused mixture of DC and tumor cells directly in their ability to induce a specific immune response.

METHODS:

Hybrids were obtained by electrofusion of tumor cells and monocyte-derived DCs. Cell phenotype was evaluated by flow cytometry and antigen-presenting ability by co-culture with syngeneic T cells followed by tetramer analysis and interferon (IFN)-γ ELISPOT.

RESULTS:

Less than half the cells in the mixture expressed DC co-stimulatory molecules. Furthermore, DCs in the mixture had significantly lower expression of MHC class I molecules than DCs in the fusion. Conversely, nearly all CD11c(+)Her2/neu(+) hybrids expressed CD80, CD86, CD83, HLA-DR and MHC class I from both tumor cells and DCs. Using tumor cells constitutively expressing a cytomegalovirus (CMV) antigen, we show that expansion of CMV-specific cytotoxic T lymphocytes (CTLs) restricted by DCs' MHC class I molecules was higher when DC-tumor hybrids were the stimulators. Furthermore, only hybrids stimulated CTLs to produce IFN-γ in response to CMV-positive target cells.

CONCLUSIONS:

These data show the superiority of DC-tumor cell hybrids over their simple mixture as T-cell stimulators. Hybrids expressed more co-stimulatory and MHC molecules, induced higher antigen-specific T-cell expansion and were the only cells able to induce IFN-γ-producing antigen-specific T cells. Thus, these data offer further support for cancer immunotherapeutic approaches using DC-tumor cell hybrids.

KEYWORDS:

cancer vaccines; cell fusion; dendritic cells; hybrid cells; immunotherapy

PMID:
26971685
DOI:
10.1016/j.jcyt.2016.01.005
[Indexed for MEDLINE]

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