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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

Mice survival. Survival of mice with melanoma inoculated with BMDCs matured with TNFα and treated with MAGE-AX, GK-1, or MAGE-AX/GK-1. The MAGE-AX/GK-1 group was the one which had a higher survival rate: 40% up to 1.5 years after being inoculated with the BMCDs. It is followed by the GK-1, MAGE-AX, TNFα, and untreated group (WT), respectively.
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fig3: Mice survival. Survival of mice with melanoma inoculated with BMDCs matured with TNFα and treated with MAGE-AX, GK-1, or MAGE-AX/GK-1. The MAGE-AX/GK-1 group was the one which had a higher survival rate: 40% up to 1.5 years after being inoculated with the BMCDs. It is followed by the GK-1, MAGE-AX, TNFα, and untreated group (WT), respectively.

Mentions: All BMDCs used in the immunotherapy were matured with TNFα and treated with (1) GK-1, (2) MAGE, or (3) MAGE-AX/GK-1. BMDC therapy started one week after inoculation of 6 × 105 B16F10 cells. Mice receiving BMDCs loaded with MAGE-AX and stimulated with GK-1 showed a higher survival rate relative to the control groups. Mice that received no therapy as well as those who received the BMDCs/TNFα treatment showed the lowest survival rate (100% death at days 24-25). The BMDCs groups treated with TNFα/MAGE-AX or GK-1 had a survival of at least 10% at day 40, while 40% of the mice that received the BMDC treatment with TNFα/MAGE-AX/GK-1 achieved a 40% survival rate up to 1.5 years after being inoculated with melanoma (Figure 3).


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)

Mice survival. Survival of mice with melanoma inoculated with BMDCs matured with TNFα and treated with MAGE-AX, GK-1, or MAGE-AX/GK-1. The MAGE-AX/GK-1 group was the one which had a higher survival rate: 40% up to 1.5 years after being inoculated with the BMCDs. It is followed by the GK-1, MAGE-AX, TNFα, and untreated group (WT), respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: Mice survival. Survival of mice with melanoma inoculated with BMDCs matured with TNFα and treated with MAGE-AX, GK-1, or MAGE-AX/GK-1. The MAGE-AX/GK-1 group was the one which had a higher survival rate: 40% up to 1.5 years after being inoculated with the BMCDs. It is followed by the GK-1, MAGE-AX, TNFα, and untreated group (WT), respectively.
Mentions: All BMDCs used in the immunotherapy were matured with TNFα and treated with (1) GK-1, (2) MAGE, or (3) MAGE-AX/GK-1. BMDC therapy started one week after inoculation of 6 × 105 B16F10 cells. Mice receiving BMDCs loaded with MAGE-AX and stimulated with GK-1 showed a higher survival rate relative to the control groups. Mice that received no therapy as well as those who received the BMDCs/TNFα treatment showed the lowest survival rate (100% death at days 24-25). The BMDCs groups treated with TNFα/MAGE-AX or GK-1 had a survival of at least 10% at day 40, while 40% of the mice that received the BMDC treatment with TNFα/MAGE-AX/GK-1 achieved a 40% survival rate up to 1.5 years after being inoculated with melanoma (Figure 3).

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