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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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Tumor development. Tumor size in mice inoculated with BMDCs matured with TNFα and treated with MAGE-AX, GK-1, or MAGE-AX/GK-1. From day 22 to day 24 the group treated with MAGE/GK-1 BMDCs had less tumor growth in comparison with all groups. From day 26 no tumor growth was shown in the TNFα and untreated groups, because the survival rate was 0%. Tumor growth of the MAGE-AX and GK-1 groups was similar. Without treatment (WT). Mean ± SEM n ≥ 3. *P < 0.05 MAGE/GK-1 versus MAGE, ∧P < 0.05 MAGE/GK-1 versus GK-1, +P < 0.001 MAGE/GK-1 versus TNF, αP < 0.001 MAGE/GK-1 versus WT.
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fig4: Tumor development. Tumor size in mice inoculated with BMDCs matured with TNFα and treated with MAGE-AX, GK-1, or MAGE-AX/GK-1. From day 22 to day 24 the group treated with MAGE/GK-1 BMDCs had less tumor growth in comparison with all groups. From day 26 no tumor growth was shown in the TNFα and untreated groups, because the survival rate was 0%. Tumor growth of the MAGE-AX and GK-1 groups was similar. Without treatment (WT). Mean ± SEM n ≥ 3. *P < 0.05 MAGE/GK-1 versus MAGE, ∧P < 0.05 MAGE/GK-1 versus GK-1, +P < 0.001 MAGE/GK-1 versus TNF, αP < 0.001 MAGE/GK-1 versus WT.

Mentions: On the other hand, the largest diameter of the tumor was measured every other day. The groups treated with TNFα/MAGE-AX or GK-1 BMDCs remained similar in size throughout the treatment, whereas untreated mice and those inoculated with TNFα BMDCs showed an increased tumor growth rate compared to the other groups. It is important to note that the group of mice that received TNFα/MAGE-AX/GK-1 BMCDs retained the lowest rate of tumor growth since the beginning of the treatment (Figure 4).


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)

Tumor development. Tumor size in mice inoculated with BMDCs matured with TNFα and treated with MAGE-AX, GK-1, or MAGE-AX/GK-1. From day 22 to day 24 the group treated with MAGE/GK-1 BMDCs had less tumor growth in comparison with all groups. From day 26 no tumor growth was shown in the TNFα and untreated groups, because the survival rate was 0%. Tumor growth of the MAGE-AX and GK-1 groups was similar. Without treatment (WT). Mean ± SEM n ≥ 3. *P < 0.05 MAGE/GK-1 versus MAGE, ∧P < 0.05 MAGE/GK-1 versus GK-1, +P < 0.001 MAGE/GK-1 versus TNF, αP < 0.001 MAGE/GK-1 versus WT.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Tumor development. Tumor size in mice inoculated with BMDCs matured with TNFα and treated with MAGE-AX, GK-1, or MAGE-AX/GK-1. From day 22 to day 24 the group treated with MAGE/GK-1 BMDCs had less tumor growth in comparison with all groups. From day 26 no tumor growth was shown in the TNFα and untreated groups, because the survival rate was 0%. Tumor growth of the MAGE-AX and GK-1 groups was similar. Without treatment (WT). Mean ± SEM n ≥ 3. *P < 0.05 MAGE/GK-1 versus MAGE, ∧P < 0.05 MAGE/GK-1 versus GK-1, +P < 0.001 MAGE/GK-1 versus TNF, αP < 0.001 MAGE/GK-1 versus WT.
Mentions: On the other hand, the largest diameter of the tumor was measured every other day. The groups treated with TNFα/MAGE-AX or GK-1 BMDCs remained similar in size throughout the treatment, whereas untreated mice and those inoculated with TNFα BMDCs showed an increased tumor growth rate compared to the other groups. It is important to note that the group of mice that received TNFα/MAGE-AX/GK-1 BMCDs retained the lowest rate of tumor growth since the beginning of the treatment (Figure 4).

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