Antigen-Specific Polyclonal Cytotoxic T Lymphocytes Induced by Fusions of Dendritic Cells and Tumor Cells

Koido, Shigeo; Homma, Sadamu; Hara, Eiichi; Namiki, Yoshihisa; Ohkusa, Toshifumi; Gong, Jianlin; Tajiri, Hisao

doi:10.1155/2010/752381

Cited by 11 publications

(14 citation statements)

References 104 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To date, several strategies have been assessed for creating DC-based cancer vaccines, including: (1) loading DCs with defined TAAs, which is the most commonly applicable strategy, for DC-based vaccination, but has a number of drawbacks [ 45 ]; (2) pulsing DCs with tumor DNA/RNA; and (3) generating fusions of DCs and tumor cells. DC/glioma-specific peptides have been confirmed to be a useful strategy to elicit CTL responses and have been shown to be more effective than other types of DC-based vaccines.…”

Section: Discussionmentioning

confidence: 99%

Human IP10-scFv and DC-induced CTL synergistically inhibit the growth of glioma in a xenograft model

et al. 2014

View full text Add to dashboard Cite

The epidermal growth factor receptor (EGFR) mutant of EGFRvIII is highly expressed in glioma cells, and the EGFRvIII-specific dendritic cell (DC)-induced tumor antigen-specific CD8+ cytotoxic T lymphocytes (CTLs) may hold promise in cancer immunotherapy. Interferon (IFN)-γ-inducible protein (IP)-10 (IP-10) is a potent inhibitor of angiogenesis and can recruit CXCR3+ T cells, including CD8+ T cells, which are important for the control of tumor growth. In this study, we assessed if the combination of IP10-EGFRvIIIscFv with DC-induced CTLs would improve the therapeutic antitumor efficacy. IP10-scFv was generated by linking the human IP-10 gene with the DNA fragment for anti-EGFRvIIIscFv with a (Gly4Ser)3 flexible linker, purified by affinity chromatography, and characterized for its anti-EGFRvIII immunoreactivity and chemotactic activity. DCs were isolated from human peripheral blood monocyte cells and pulsed with EGFRvIII-peptide, then co-cultured with autologous CD8+ T cells. BALB/c-nu mice were inoculated with human glioma U87-EGFRvIII cells in the brain and treated intracranially with IP10-scFv and/or intravenously with DC-induced CTLs for evaluating the therapeutic effect. Treatment with both IP10-scFv and EGFRvIII peptide-pulsed, DC-induced CTL synergistically inhibited the growth of glioma and prolonged the survival of tumor-bearing mice, which was accompanied by the inhibition of tumor angiogenesis and enhancement of cytotoxicity, thereby increasing the numbers of brain-infiltrating lymphocytes (BILs) and prolonging the residence time of CTLs in the tumor.

show abstract

Section: Discussionmentioning

confidence: 99%

Human IP10-scFv and DC-induced CTL synergistically inhibit the growth of glioma in a xenograft model

et al. 2014

View full text Add to dashboard Cite

show abstract

“…These cells possibly express all TAs and combine it with the immune stimulatory capacities of APCs ( 17 , 42 ). Immunity might be enhanced because different TAs may induce different immune effector mechanisms ( 50 , 51 ). Upon establishment of a vaccination protocol, the generation of tumor/DC-fusion hybrids may thus result in a simple form of personalized anti-cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Immune responses induced by fusion hybrids have mainly been associated with the induction of tumor-specific CTLs ( 51 ). We additionally observed a marked humoral immune response, which could contribute to efficient anti-tumor responses.…”

Section: Discussionmentioning

confidence: 99%

Adaptive Resistance to Immunotherapy Directed Against p53 Can be Overcome by Global Expression of Tumor-Antigens in Dendritic Cells

Humar

Azémar²,

Maurer

et al. 2014

Front. Oncol.

View full text Add to dashboard Cite

Immunotherapy of cancer utilizes dendritic cells (DCs) for antigen presentation and the induction of tumor-specific immune responses. However, the therapeutic induction of anti-tumor immunity is limited by tumor escape mechanisms. In this study, immortalized dendritic D2SC/1 cells were transduced with a mutated version of the p53 tumor suppressor gene, p53M234I, or p53C132F/E168G, which are overexpressed in MethA fibrosarcoma tumor cells. In addition, D2SC/1 cells were fused with MethA tumor cells to generate a vaccine that potentially expresses a large repertoire of tumor-antigens. Cellular vaccines were transplanted onto Balb/c mice and MethA tumor growth and anti-tumor immune responses were examined in vaccinated animals. D2SC/1–p53M234I and D2SC/1–p53C132F/E168G cells induced strong therapeutic and protective MethA tumor immunity upon transplantation in Balb/c mice. However, in a fraction of immunized mice MethA tumor growth resumed after an extended latency period. Analysis of these tumors indicated loss of p53 expression. Mice, pre-treated with fusion hybrids generated from D2SC/1 and MethA tumor cells, suppressed MethA tumor growth and averted adaptive immune escape. Polyclonal B-cell responses directed against various MethA tumor proteins could be detected in the sera of D2SC/1–MethA inoculated mice. Athymic nude mice and Balb/c mice depleted of CD4+ or CD8+ T-cells were not protected against MethA tumor cell growth after immunization with D2SC/1–MethA hybrids. Our results highlight a potential drawback of cancer immunotherapy by demonstrating that the induction of a specific anti-tumor response favors the acquisition of tumor phenotypes promoting immune evasion. In contrast, the application of DC/tumor cell fusion hybrids prevents adaptive immune escape by a T-cell dependent mechanism and provides a simple strategy for personalized anti-cancer treatment without the need of selectively priming the host immune system.

show abstract

“…The strategy for DC/tumor fusion vaccine is based on the fact that DCs are the most potent antigen-presenting cells in the body, whereas tumor cells express abundant tumor antigens. In animal studies, DC/tumor fusion vaccines have been shown to possess the elements essential for processing and presenting tumor antigens to host immune cells, for inducing effective immune response, and for breaking T-cell tolerance to TAAs (Gong, Chen et al, 1997;Koido, Hara et al, 2007;Gong, Koido et al, 2008;Koido, Hara et al, 2009;Koido, Hara et al, 2010a;Koido, Homma et al, 2010b). Recently, we have reported that fusions of human pancreatic cancer cells and DCs induce CTL responses against pancreatic cancer cells in vitro (Koido, Hara et al, 2010a).…”

Section: Dc-based Vaccinesmentioning

confidence: 99%

Immunotherapy for Pancreatic Cancer

Koido¹,

Homma²,

Takahara³

et al. 2012

Pancreatic Cancer - Molecular Mechanism and Targets

Self Cite

View full text Add to dashboard Cite

Antigen-Specific Polyclonal Cytotoxic T Lymphocytes Induced by Fusions of Dendritic Cells and Tumor Cells

Cited by 11 publications

References 104 publications

Human IP10-scFv and DC-induced CTL synergistically inhibit the growth of glioma in a xenograft model

Human IP10-scFv and DC-induced CTL synergistically inhibit the growth of glioma in a xenograft model

Adaptive Resistance to Immunotherapy Directed Against p53 Can be Overcome by Global Expression of Tumor-Antigens in Dendritic Cells

Immunotherapy for Pancreatic Cancer

Contact Info

Product

Resources

About