2006Journal of Nantong UniversityRequires access

An experimental study on induction of lung cancer specific immune response by vaccination of freeze-thaw cell lysate-pulsed dendritic cells

Shaoming Zhang

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Abstract

Objective:To make use of the characteristics of presenting and processing tumor antigen of dendritic cells to enhance killing capability of CTL against lung cancer.Methods:Autologous dendritic cells were isolated from PBMC and then stimulated in vitro with granulocyte-macrophage colony-stimulating factor(GM-CSF) and interleukin-4(IL-4).Dendritic cells were loaded with A549 tumor cell freeze-thaw lysate;at the same time Hsp70L1 as an immunol adjuvant was added.The specific groupings each induce generation of tumor specific cytotoxic T cells(CTLs).Killing activity and cytokine release of the CTL and the population of CTL were measured by cytotoxic assay and ELISA and FACS analyses.Results:DCs pulsed with A549 tumor cell lysate can enhance the growth expansion of CTL;up-regulation of the CD3+ and CD8+ population in CTL as well as an augmentation of Th1 cytokines;the cytotoxicity of specific CTL against A549 was highly enhanced;The above indications become more obvious after the addition of Hsp70L1.Conclusion:These results indicate that DCs can process and present tumor antigen to stimulate generation of specific CTL and with the addition of Hsp70L1,this activity can be further enhanced.It is suggested that DCs possess a clinically useful prospect of vaccines and specific CTL adoptive immunotherapy in patient with lung cancer.

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Objective:To make use of the characteristics of presenting and processing tumor antigen of dendritic cells to enhance killing capability of CTL against lung cancer.Methods:Autologous dendritic cells were isolated from PBMC and then stimulated in vitro with granulocyte-macrophage colony-stimulating factor(GM-CSF) and interleukin-4(IL-4).Dendritic cells were loaded with A549 tumor cell freeze-thaw lysate;at the same time Hsp70L1 as an immunol adjuvant was added.The specific groupings each induce generation of tumor specific cytotoxic T cells(CTLs).Killing activity and cytokine release of the CTL and the population of CTL were measured by cytotoxic assay and ELISA and FACS analyses.Results:DCs pulsed with A549 tumor cell lysate can enhance the growth expansion of CTL;up-regulation of the CD3+ and CD8+ population in CTL as well as an augmentation of Th1 cytokines;the cytotoxicity of specific CTL against A549 was highly enhanced;The above indications become more obvious after the addition of Hsp70L1.Conclusion:These results indicate that DCs can process and present tumor antigen to stimulate generation of specific CTL and with the addition of Hsp70L1,this activity can be further enhanced.It is suggested that DCs possess a clinically useful prospect of vaccines and specific CTL adoptive immunotherapy in patient with lung cancer.

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Available abstract

Objective:To make use of the characteristics of presenting and processing tumor antigen of dendritic cells to enhance killing capability of CTL against lung cancer.Methods:Autologous dendritic cells were isolated from PBMC and then stimulated in vitro with granulocyte-macrophage colony-stimulating factor(GM-CSF) and interleukin-4(IL-4).Dendritic cells were loaded with A549 tumor cell freeze-thaw lysate;at the same time Hsp70L1 as an immunol adjuvant was added.The specific groupings each induce generation of tumor specific cytotoxic T cells(CTLs).Killing activity and cytokine release of the CTL and the population of CTL were measured by cytotoxic assay and ELISA and FACS analyses.Results:DCs pulsed with A549 tumor cell lysate can enhance the growth expansion of CTL;up-regulation of the CD3+ and CD8+ population in CTL as well as an augmentation of Th1 cytokines;the cytotoxicity of specific CTL against A549 was highly enhanced;The above indications become more obvious after the addition of Hsp70L1.Conclusion:These results indicate that DCs can process and present tumor antigen to stimulate generation of specific CTL and with the addition of Hsp70L1,this activity can be further enhanced.It is suggested that DCs possess a clinically useful prospect of vaccines and specific CTL adoptive immunotherapy in patient with lung cancer.

Key concepts: CTL*, Cytotoxic T cell, Dendritic cell, Immunology, CD8, Immune system, Immunotherapy, Antigen

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