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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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Specific cytotoxic T lymphocyte (CTL)-mediated lysis of various target cells in vitro and ex vivo by CTL generated from different heparanase-derived peptides. (A) Specific lysis of CTL induced by multi-epitope vaccines or the single epitope-pulsed dendritic cells derived from PBMC against KATO-III (a, b), U2OS (c, d) and SW480 (e, f) cells. (B) Specific lysis of CTL induced by multi-epitope vaccines or the single epitope-pulsed dendritic cells derived from HLA-A2 transgenic mice bone marrow against KATO-III (a, b), U2OS (c, d) and SW480 (e, f) cells. The CTL generated from the HIVpol(476-484)(ILLEPVHGV) peptide derived from HIV served as the negative peptide control (NP). E/T, effector/target.
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fig03: Specific cytotoxic T lymphocyte (CTL)-mediated lysis of various target cells in vitro and ex vivo by CTL generated from different heparanase-derived peptides. (A) Specific lysis of CTL induced by multi-epitope vaccines or the single epitope-pulsed dendritic cells derived from PBMC against KATO-III (a, b), U2OS (c, d) and SW480 (e, f) cells. (B) Specific lysis of CTL induced by multi-epitope vaccines or the single epitope-pulsed dendritic cells derived from HLA-A2 transgenic mice bone marrow against KATO-III (a, b), U2OS (c, d) and SW480 (e, f) cells. The CTL generated from the HIVpol(476-484)(ILLEPVHGV) peptide derived from HIV served as the negative peptide control (NP). E/T, effector/target.

Mentions: Next, we assessed the killing effect of lymphocytes induced by all of the predicted epitopes. Our results showed that Hpa16, Hpa8, Hpa310, Hpa315 and Hpa363 were able to elicit an effective antitumor immune response (Fig.2). To detect whether the heparanase multi-epitope vaccines could elicit stronger heparanase-specific CTL than the corresponding single heparanase peptides vaccines, DC were loaded with heparanase multi-epitope vaccines and their corresponding single peptides to induce heparanase-specific CTL. The cytotoxicity of heparanase-specific CTLs to various tumor cell lines was measured using a 4-h 51Cr release assay. The results showed that the multi-epitope vaccines from human heparanase Hpa525 + 277 + 405 + 16 and Hpa8 + 310 + 315 + 363 and their corresponding single peptides Hpa525, Hpa277, Hpa405, Hpa16, Hpa8, Hpa310, Hpa315 and Hpa363 could induce heparanase-specific killing of KATO-III gastric cancer cells, U2OS osteogenic sarcoma cells and SW480 colonic cancer cells, which express both heparanase and HLA-A2 (Fig.3). At the highest E/T ratio (80:1), the lysis rates of CTL generated from Ad-Hpa were 85.3% in vitro and 79.6% ex vivo. The lysis rates of CTL generated from the multi-epitope vaccines were 73.9%, 71.1% and 74.4%, respectively, in vitro and 68.5%, 67.6%, and 67.8%, respectively, ex vivo. The highest lysis rates of CTL generated from Hpa525, Hpa277, Hpa405, Hpa16, Hpa8, Hpa310, Hpa315 and Hpa363 were 58.2%, in vitro and 54.3%, ex vivo. The induced effector cells generated from the negative peptide could not lyse the target cells. These results indicate that multi-epitope vaccines generated from human heparanase are capable of eliciting much more potent killing of tumor cells than their corresponding single peptides in vitro and ex vivo (Fig.3).


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)

Specific cytotoxic T lymphocyte (CTL)-mediated lysis of various target cells in vitro and ex vivo by CTL generated from different heparanase-derived peptides. (A) Specific lysis of CTL induced by multi-epitope vaccines or the single epitope-pulsed dendritic cells derived from PBMC against KATO-III (a, b), U2OS (c, d) and SW480 (e, f) cells. (B) Specific lysis of CTL induced by multi-epitope vaccines or the single epitope-pulsed dendritic cells derived from HLA-A2 transgenic mice bone marrow against KATO-III (a, b), U2OS (c, d) and SW480 (e, f) cells. The CTL generated from the HIVpol(476-484)(ILLEPVHGV) peptide derived from HIV served as the negative peptide control (NP). E/T, effector/target.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig03: Specific cytotoxic T lymphocyte (CTL)-mediated lysis of various target cells in vitro and ex vivo by CTL generated from different heparanase-derived peptides. (A) Specific lysis of CTL induced by multi-epitope vaccines or the single epitope-pulsed dendritic cells derived from PBMC against KATO-III (a, b), U2OS (c, d) and SW480 (e, f) cells. (B) Specific lysis of CTL induced by multi-epitope vaccines or the single epitope-pulsed dendritic cells derived from HLA-A2 transgenic mice bone marrow against KATO-III (a, b), U2OS (c, d) and SW480 (e, f) cells. The CTL generated from the HIVpol(476-484)(ILLEPVHGV) peptide derived from HIV served as the negative peptide control (NP). E/T, effector/target.
Mentions: Next, we assessed the killing effect of lymphocytes induced by all of the predicted epitopes. Our results showed that Hpa16, Hpa8, Hpa310, Hpa315 and Hpa363 were able to elicit an effective antitumor immune response (Fig.2). To detect whether the heparanase multi-epitope vaccines could elicit stronger heparanase-specific CTL than the corresponding single heparanase peptides vaccines, DC were loaded with heparanase multi-epitope vaccines and their corresponding single peptides to induce heparanase-specific CTL. The cytotoxicity of heparanase-specific CTLs to various tumor cell lines was measured using a 4-h 51Cr release assay. The results showed that the multi-epitope vaccines from human heparanase Hpa525 + 277 + 405 + 16 and Hpa8 + 310 + 315 + 363 and their corresponding single peptides Hpa525, Hpa277, Hpa405, Hpa16, Hpa8, Hpa310, Hpa315 and Hpa363 could induce heparanase-specific killing of KATO-III gastric cancer cells, U2OS osteogenic sarcoma cells and SW480 colonic cancer cells, which express both heparanase and HLA-A2 (Fig.3). At the highest E/T ratio (80:1), the lysis rates of CTL generated from Ad-Hpa were 85.3% in vitro and 79.6% ex vivo. The lysis rates of CTL generated from the multi-epitope vaccines were 73.9%, 71.1% and 74.4%, respectively, in vitro and 68.5%, 67.6%, and 67.8%, respectively, ex vivo. The highest lysis rates of CTL generated from Hpa525, Hpa277, Hpa405, Hpa16, Hpa8, Hpa310, Hpa315 and Hpa363 were 58.2%, in vitro and 54.3%, ex vivo. The induced effector cells generated from the negative peptide could not lyse the target cells. These results indicate that multi-epitope vaccines generated from human heparanase are capable of eliciting much more potent killing of tumor cells than their corresponding single peptides in vitro and ex vivo (Fig.3).

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