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GK-1 improves the immune response induced by bone marrow dendritic cells loaded with MAGE-AX in mice with melanoma.

Piñón-Zárate G, Herrera-Enríquez MÁ, Hernández-Téllez B, Jarquín-Yáñez K, Castell-Rodríguez AE - J Immunol Res (2014)

Bottom Line: Immunostimulants that could drive a desired immune response are necessary to be found in order to generate a long lasting tumor immune response.Besides, the treatment helped to increase CD8 lymphocytes levels and to produce IFNγ in lymph nodes.Moreover, the histopathological analysis showed that BMDCs treated with GK-1/TNFα and loaded with MAGE-AX induced the apparition of more apoptotic and necrotic areas in tumors than in mice without treatment.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio de Inmunoterapia e Ingeniería de Tejidos, Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autónoma de México Edificio A, Sexto Piso, Ciudad Universitaria, Avenida Universidad No. 3000, Ciudad de México 04510DF, Mexico.

ABSTRACT
The aim of dendritic cell (DC) vaccination in cancer is to induce tumor-specific effector T cells that may reduce and control tumor mass. Immunostimulants that could drive a desired immune response are necessary to be found in order to generate a long lasting tumor immune response. GK-1 peptide, derived from Taenia crassiceps, induces not only increase in TNFα, IFNγ, and MCP-1 production in cocultures of DCs and T lymphocytes but also immunological protection against influenza virus. Moreover, the aim of this investigation is the use of GK-1 as a bone marrow DCs (BMDCs) immunostimulant targeted with MAGE antigen; thus, BMDC may be used as immunotherapy against murine melanoma. GK-1 induced in BMDCs a meaningful increment of CD86 and IL-12. In addition, the use of BMDCs TNFα/GK-1/MAGE-AX induced the highest survival and the smallest tumors in mice. Besides, the treatment helped to increase CD8 lymphocytes levels and to produce IFNγ in lymph nodes. Moreover, the histopathological analysis showed that BMDCs treated with GK-1/TNFα and loaded with MAGE-AX induced the apparition of more apoptotic and necrotic areas in tumors than in mice without treatment. These results highlight the properties of GK-1 as an immunostimulant of DCs and suggest as a potential candidate the use of this immunotherapy against cancer disease.

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Related in: MedlinePlus

Effect of GK-1 and/or MAGE-AX with TNFα in the BMDCs phenotype. Treatment with MAGE-AX did not induce changes in the phenotype of BMDCs. (a) Percentage of CD40+ BMDCs. *P < 0.05. (b) MFI of CD40 in BMDCs. *P < 0.05. (c) Percentage of CD86+ BMDCs. **P < 0.001. (d) MFI of CD86 in BMDCs. **P < 0.05, ***P < 0.001. (e) Percentage of CD80+ BMDCs. *P < 0.05. (f) MFI of CD80 in BMDCs. *P < 0.05. Mean ± SEM n ≥ 3.
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fig2: Effect of GK-1 and/or MAGE-AX with TNFα in the BMDCs phenotype. Treatment with MAGE-AX did not induce changes in the phenotype of BMDCs. (a) Percentage of CD40+ BMDCs. *P < 0.05. (b) MFI of CD40 in BMDCs. *P < 0.05. (c) Percentage of CD86+ BMDCs. **P < 0.001. (d) MFI of CD86 in BMDCs. **P < 0.05, ***P < 0.001. (e) Percentage of CD80+ BMDCs. *P < 0.05. (f) MFI of CD80 in BMDCs. *P < 0.05. Mean ± SEM n ≥ 3.

Mentions: MAGE-AX was used as a tumor antigen to induce a specific response against melanoma, so also it was verified whether exposure to MAGE-AX could induce a change in the expression of MHCII and costimulatory molecules. The BMDCs phenotype matured with TNFα with or without GK-1 and MAGE-AX showed no significant changes in the MFI of costimulatory molecules or in the percentage of positive BMDCs to these molecules (Figure 2).


GK-1 improves the immune response induced by bone marrow dendritic cells loaded with MAGE-AX in mice with melanoma.

Piñón-Zárate G, Herrera-Enríquez MÁ, Hernández-Téllez B, Jarquín-Yáñez K, Castell-Rodríguez AE - J Immunol Res (2014)

Effect of GK-1 and/or MAGE-AX with TNFα in the BMDCs phenotype. Treatment with MAGE-AX did not induce changes in the phenotype of BMDCs. (a) Percentage of CD40+ BMDCs. *P < 0.05. (b) MFI of CD40 in BMDCs. *P < 0.05. (c) Percentage of CD86+ BMDCs. **P < 0.001. (d) MFI of CD86 in BMDCs. **P < 0.05, ***P < 0.001. (e) Percentage of CD80+ BMDCs. *P < 0.05. (f) MFI of CD80 in BMDCs. *P < 0.05. Mean ± SEM n ≥ 3.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4230216&req=5

fig2: Effect of GK-1 and/or MAGE-AX with TNFα in the BMDCs phenotype. Treatment with MAGE-AX did not induce changes in the phenotype of BMDCs. (a) Percentage of CD40+ BMDCs. *P < 0.05. (b) MFI of CD40 in BMDCs. *P < 0.05. (c) Percentage of CD86+ BMDCs. **P < 0.001. (d) MFI of CD86 in BMDCs. **P < 0.05, ***P < 0.001. (e) Percentage of CD80+ BMDCs. *P < 0.05. (f) MFI of CD80 in BMDCs. *P < 0.05. Mean ± SEM n ≥ 3.
Mentions: MAGE-AX was used as a tumor antigen to induce a specific response against melanoma, so also it was verified whether exposure to MAGE-AX could induce a change in the expression of MHCII and costimulatory molecules. The BMDCs phenotype matured with TNFα with or without GK-1 and MAGE-AX showed no significant changes in the MFI of costimulatory molecules or in the percentage of positive BMDCs to these molecules (Figure 2).

Bottom Line: Immunostimulants that could drive a desired immune response are necessary to be found in order to generate a long lasting tumor immune response.Besides, the treatment helped to increase CD8 lymphocytes levels and to produce IFNγ in lymph nodes.Moreover, the histopathological analysis showed that BMDCs treated with GK-1/TNFα and loaded with MAGE-AX induced the apparition of more apoptotic and necrotic areas in tumors than in mice without treatment.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio de Inmunoterapia e Ingeniería de Tejidos, Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autónoma de México Edificio A, Sexto Piso, Ciudad Universitaria, Avenida Universidad No. 3000, Ciudad de México 04510DF, Mexico.

ABSTRACT
The aim of dendritic cell (DC) vaccination in cancer is to induce tumor-specific effector T cells that may reduce and control tumor mass. Immunostimulants that could drive a desired immune response are necessary to be found in order to generate a long lasting tumor immune response. GK-1 peptide, derived from Taenia crassiceps, induces not only increase in TNFα, IFNγ, and MCP-1 production in cocultures of DCs and T lymphocytes but also immunological protection against influenza virus. Moreover, the aim of this investigation is the use of GK-1 as a bone marrow DCs (BMDCs) immunostimulant targeted with MAGE antigen; thus, BMDC may be used as immunotherapy against murine melanoma. GK-1 induced in BMDCs a meaningful increment of CD86 and IL-12. In addition, the use of BMDCs TNFα/GK-1/MAGE-AX induced the highest survival and the smallest tumors in mice. Besides, the treatment helped to increase CD8 lymphocytes levels and to produce IFNγ in lymph nodes. Moreover, the histopathological analysis showed that BMDCs treated with GK-1/TNFα and loaded with MAGE-AX induced the apparition of more apoptotic and necrotic areas in tumors than in mice without treatment. These results highlight the properties of GK-1 as an immunostimulant of DCs and suggest as a potential candidate the use of this immunotherapy against cancer disease.

Show MeSH
Related in: MedlinePlus