Study on <em>in vitro</em> antitumor immune responses elicited by dendritic cells pulsed with heparanase multiple antigen peptides containing cytotoxic T lymphocyte epitopes

Wang Guozhen; Tang Xudong; Wu Yuyun; Li Ning; Li Changzhu; Chen Ling; Fang Dianchun; Yang Shiming

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Study on in vitro antitumor immune responses elicited by dendritic cells pulsed with heparanase multiple antigen peptides containing cytotoxic T lymphocyte epitopes

更新时间：2025-01-15

- Study on in vitro antitumor immune responses elicited by dendritic cells pulsed with heparanase multiple antigen peptides containing cytotoxic T lymphocyte epitopes
- Journal of Army Medical University Vol. 33, Issue 8, Pages: 761-764(2011)
- 作者机构：
  
  第三军医大学西南医院全军消化病研究所
- 作者简介：
- 基金信息：
- DOI：
  CLC： R73-362;R392.2;{R392.13}
- Published：2011，
  
  Published Online：30 April 2011，
- 稿件说明：
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WANG GUOZHEN, TANG XUDONG, WU YUYUN, et al. Study on in vitro antitumor immune responses elicited by dendritic cells pulsed with heparanase multiple antigen peptides containing cytotoxic T lymphocyte epitopes. [J]. Journal of army medical university, 2011, 33(8): 761-764.
DOI：

WANG GUOZHEN, TANG XUDONG, WU YUYUN, et al. Study on in vitro antitumor immune responses elicited by dendritic cells pulsed with heparanase multiple antigen peptides containing cytotoxic T lymphocyte epitopes. [J]. Journal of army medical university, 2011, 33(8): 761-764. DOI：

摘要

目的研究肝素酶（heparanase，Hpa）细胞毒T淋巴细胞（cytotoxic T lymphocyte，CTL）表位多抗原肽（multiple antigen peptides，MAP）疫苗能否诱导更强的Hpa特异性CTL反应。方法 HLA-A2.1限制性肝素酶CTL表位多抗原肽负载正常人外周血来源（peripheral blood mononuclear cell，PBMC）树突状细胞（dendritic cell，DC），诱导CTL，采用4 h标准

Cr释放实验检测上述CTL对不同肿瘤细胞的免疫杀伤效应；采用ELISPOT实验检测效应细胞分泌IFN-γ的能力。结果肝素酶CTL表位MAP疫苗诱导的CTL对Hpa阳性且HLA-A2.1匹配的KATO-Ⅲ胃癌细胞、U2OS骨肉瘤细胞、SW480结肠癌细胞具有杀伤效应，且其杀伤效应强于相应的单肽，在最大效应细胞/靶细胞(effector/target

E/T) 时高出率均大于16%；其对HLA-A2.1阴性的HepG2肝癌细胞和Hpa阴性的MCF-7乳腺癌细胞不具有杀伤效应，但是对MCF-7/Hpa乳腺癌细胞和HepG2/HLA-A2肝癌细胞具有杀伤效应，且其杀伤效应强于相应的单肽，在最大E/T时高出率均大于18%；其对自体淋巴细胞和DC 不具有杀伤效应。另一方面人肝素酶CTL表位MAP疫苗诱导的IFN-γ分泌水平强于相应的单肽。结论肝素酶CTL表位MAP疫苗能激发较相应单肽更强的特异性和非特异性抗肿瘤效应。

Abstract

Objective To study whether the multiple antigen peptides (MAPs) of heparanase (Hpa) can elicit stronger Hpa-specific cytotoxic T lymphocyte (CTL) responses against various tumors

in vitro

. Methods Dendritic cells (DCs) were pulsed with HLA-A2.1-restricted Hpa MAPs an

d Hpa single peptides to induce Hpa-specific CTLs. The lysis of KATO-Ⅲ gastric cancer cells

U2OS osteogenic sarcoma cells

SW480 colon cancer cells

HepG2 liver cancer cells

MCF-7 breast cancer cells

HepG2/HLA-A2.1 liver cancer cells

and MCF-7/Hpa breast cancer cells by Hpa-specific CTLs was examined by 4-h standard

Cr release assay. The IFN-γ production of the effector cells was tested with ELISPOT. Results Compared with those induced by Hpa single peptides

the CTLs induced by Hpa MAPs had stronger specific lysis effects on Hpa- and HLA-A2.1-positive tumor cells (KATO-Ⅲ

U2OS

and SW480)

by more than 16% at the maximum effector/target (E/T) ratio. Neither Hpa-negative MCF-7 cells nor HLA-A2.1-negative HepG2 cells were lysed by the CTLs. The effector cells induced by Hpa MAPs

however

could lyse HepG2/HLA-A2.1 cells (HLA-A2.1-positive) and MCF-7/Hpa cells (Hpa-positive)

and had stronger specific lysis effects than those induced by Hpa single peptides

by more than 18% at the maximum E/T ratio. Hpa MAPs could not elicit lysis of auto-logous lymphocytes and DCs. Compared with Hpa single peptides

Hpa MAPs could increase the frequency of IFN-γ-producing T cells. Conclusions This study shows that Hpa MAPs can elicit stronger specific and nonspecific antitumor immune responses by Hpa-specific CTLs.

关键词

肝素酶CTL表位多抗原肽树突状细胞肿瘤疫苗

Keywords

heparanaseCTL epitopesmultiple antigen peptidedendritic cellstumor vaccine

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Study on in vitro antitumor immune responses elicited by dendritic cells pulsed with heparanase multiple antigen peptides containing cytotoxic T lymphocyte epitopes

DOI：

摘要

Abstract

关键词

Keywords

references