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In vitro and ex vivo evaluation of a multi-epitope heparinase vaccine for various malignancies.

Tang XD, Guo SL, Wang GZ, Li N, Wu YY, Fang DC, Fan YH, Yang SM - Cancer Sci. (2013)

Bottom Line: Previous studies have indicated that heparanase (Hpa) might represent a candidate universal tumor-associated antigen.The results showed that multi-epitope vaccines Hpa525 + 277 + 405 + 16 and Hpa8 + 310 + 315 + 363 induced higher Hpa-specific lysis of various cancer cells from different tissues in a HLA-A2-restricted and heparanase-specific manner compared with the single epitope vaccines Hpa525, Hpa277, Hpa405, Hpa16, Hpa8, Hpa310, Hpa315 and Hpa363, both in vitro and ex vivo.Therefore, the present study provides theoretical evidence for the use of heparanase multi-epitope vaccines for clinical application.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China; Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China.

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Western blot analysis of dendritic cells (DC) and lymphocyte for heparanase expression and heparanase-specific cytotoxic T lymphocyte (CTL) killing of autologous lymphocytes and DC in vitro and ex vivo. (A) Western blot analysis of DC and lymphocyte for heparanase expression. (1) Heparanase expression in lymphocytes. (2) Heparanase expression in dendritic cells. (B, C) The CTL generated from the HLA-A2-restricted nonapeptide HIVpol(476-484)(ILLEPVHGV) derived from HIV serves as the negative peptide control (NP). The KATO-III cells serve as a target for the positive control (PC). Specific lysis of CTL generated from heparanase multi-epitope vaccines and single epitope peptides against autologous lymphocytes and DC in vitro (B) and ex vivo (C).
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fig05: Western blot analysis of dendritic cells (DC) and lymphocyte for heparanase expression and heparanase-specific cytotoxic T lymphocyte (CTL) killing of autologous lymphocytes and DC in vitro and ex vivo. (A) Western blot analysis of DC and lymphocyte for heparanase expression. (1) Heparanase expression in lymphocytes. (2) Heparanase expression in dendritic cells. (B, C) The CTL generated from the HLA-A2-restricted nonapeptide HIVpol(476-484)(ILLEPVHGV) derived from HIV serves as the negative peptide control (NP). The KATO-III cells serve as a target for the positive control (PC). Specific lysis of CTL generated from heparanase multi-epitope vaccines and single epitope peptides against autologous lymphocytes and DC in vitro (B) and ex vivo (C).

Mentions: Heparanase is expressed in immunologically competent cells, natural killer cells and inflammatory cells such as neutrophils, granulocytes and activated T and B cells.25 Theoretically, immunotherapy targeting heparanase might have side-effects on the immune system. To investigate the effect of heparanase-specific CTL on immunologically activated lymphocytes, CTL induced by heparanase-specific peptides were also used to lyse autologous lymphocytes and DC. The results indicate that multi-epitope vaccines and their corresponding single peptides from heparanase did not lyse autologous lymphocytes or DC in vitro or ex vivo (Fig.5).


In vitro and ex vivo evaluation of a multi-epitope heparinase vaccine for various malignancies.

Tang XD, Guo SL, Wang GZ, Li N, Wu YY, Fang DC, Fan YH, Yang SM - Cancer Sci. (2013)

Western blot analysis of dendritic cells (DC) and lymphocyte for heparanase expression and heparanase-specific cytotoxic T lymphocyte (CTL) killing of autologous lymphocytes and DC in vitro and ex vivo. (A) Western blot analysis of DC and lymphocyte for heparanase expression. (1) Heparanase expression in lymphocytes. (2) Heparanase expression in dendritic cells. (B, C) The CTL generated from the HLA-A2-restricted nonapeptide HIVpol(476-484)(ILLEPVHGV) derived from HIV serves as the negative peptide control (NP). The KATO-III cells serve as a target for the positive control (PC). Specific lysis of CTL generated from heparanase multi-epitope vaccines and single epitope peptides against autologous lymphocytes and DC in vitro (B) and ex vivo (C).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317872&req=5

fig05: Western blot analysis of dendritic cells (DC) and lymphocyte for heparanase expression and heparanase-specific cytotoxic T lymphocyte (CTL) killing of autologous lymphocytes and DC in vitro and ex vivo. (A) Western blot analysis of DC and lymphocyte for heparanase expression. (1) Heparanase expression in lymphocytes. (2) Heparanase expression in dendritic cells. (B, C) The CTL generated from the HLA-A2-restricted nonapeptide HIVpol(476-484)(ILLEPVHGV) derived from HIV serves as the negative peptide control (NP). The KATO-III cells serve as a target for the positive control (PC). Specific lysis of CTL generated from heparanase multi-epitope vaccines and single epitope peptides against autologous lymphocytes and DC in vitro (B) and ex vivo (C).
Mentions: Heparanase is expressed in immunologically competent cells, natural killer cells and inflammatory cells such as neutrophils, granulocytes and activated T and B cells.25 Theoretically, immunotherapy targeting heparanase might have side-effects on the immune system. To investigate the effect of heparanase-specific CTL on immunologically activated lymphocytes, CTL induced by heparanase-specific peptides were also used to lyse autologous lymphocytes and DC. The results indicate that multi-epitope vaccines and their corresponding single peptides from heparanase did not lyse autologous lymphocytes or DC in vitro or ex vivo (Fig.5).

Bottom Line: Previous studies have indicated that heparanase (Hpa) might represent a candidate universal tumor-associated antigen.The results showed that multi-epitope vaccines Hpa525 + 277 + 405 + 16 and Hpa8 + 310 + 315 + 363 induced higher Hpa-specific lysis of various cancer cells from different tissues in a HLA-A2-restricted and heparanase-specific manner compared with the single epitope vaccines Hpa525, Hpa277, Hpa405, Hpa16, Hpa8, Hpa310, Hpa315 and Hpa363, both in vitro and ex vivo.Therefore, the present study provides theoretical evidence for the use of heparanase multi-epitope vaccines for clinical application.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China; Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China.

Show MeSH
Related in: MedlinePlus