|Induction of cytotoxic T lymphocytes from the peripheral blood of a hepatocellular carcinoma patient using melanoma antigen-1 (MAGE-1) peptide|
|Lu, JF; Leng, XS; Peng, JR; Mou, DC; Pang, XW; Shang, XY; Chen, WF|
|关键词||MAGE-1 cytotoxic T lymphocytes hepatocellular carcinoma immunotherapy|
|刊名||CHINESE MEDICAL JOURNAL|
|WOS标题词||Science & Technology|
|类目[WOS]||Medicine, General & Internal|
|研究领域[WOS]||General & Internal Medicine|
Objective To investigate the possibility of using melanoma antigen-1 (MAGE-1) peptide as a tumor vaccine to treat hepatocellular carcinoma ( HCC).
Methods The expressions of MAGE-1 in 8 HCC cell lines and in liver cancer tissue from a patient were detected using RT-PCR. The type of human leucocyte antigen I (HLA I) of both 8 HCC cell lines and peripheral blood mononuclear cells of the patient was detected using a microcytotoxicity method to screen out target cell lines for the cytotoxicity assay. Peripheral blood mononuclear cells from the HCC patient pulsed with an MAGE-1 pepticle ( NYKCRFPEI) were used as antigen presenting cells. Autogenous peripheral blood mononuclear cells were stimulated with antigen presenting cells every 7 days for 4 times to elicit cytotoxic T lymphocytes. The phenotype of effector cells was analyzed using flow cytometry. The cytotoxicity of effector cells was detected with a lactate dehydrogenase releasing assay.
Results The expressions of both MAGE-1 and HLA-A24 were detected in BEL7405 cell line which were used as the positive target cell line in the cytotoxicity assay. The expression of MAGE-1 alone was detected in HLE, BEL7402, BEL7404, QGY7703 and SMMC7721 cell lines, and the expression of neither MAGE-1 nor HLA-A24 was shown in QGY 7701 and HpG2 cell lines. The last 7 cell lines could be used as negative target cell lines in the cytotoxicity assay. Peripheral blood mononuclear cells expanded 32 folds during 28-day culture. The ratio of CD3(+) T cells increased by 16% (from 54% to 70%), and the ratio of CD8(+) T cells increased by 20% (from 36% to 56%) during 28-day culture. When the ratio of effector cells to target cells was 10: 1, effector cells exhibited 62.5% cytotoxicity against autogenous lymphoblasts pulsed with the peptide (NYKCRFPEI) of MAGE-1 antigen, 40.25% cytotoxicity against BEL7405 cells, compared with 17.88% cytolysis observed against autogenous lymphoblasts, 19.55% against HLE cells, and 1.6% against QGY7701 cells. When the ratio of effector cells to target cells was 3. 3:1, the cytotoxicity of effector cells against the peptide pulsed autogenous lymphoblasts was 53.6%, which was much higher against autogenous lymphoblasts, HLE cells and QGY7701 cells at 15.6%, 13% and 1%, respectively.
Conclusion The results demonstrate that cytotoxic T lymphocytes with the ability to specifically lyse target cells expressing both MAGE-1 and HLA-A24 could be successfully induced by the MAGE-1 peptide NYKCRFPEI in vitro. This indicates that a good result might be anticipated if this peptide is used as a tumor vaccine to treat HLA-A24 HCC patients.
|作者单位||1.Peking Univ, Peoples Hosp, Dept Hepatobiliary Surg, Beijing 100044, Peoples R China|
2.Peking Univ, Hlth Sci Ctr, Dept Immunol, Beijing 100044, Peoples R China
3.Zhengzhou Univ, Dept Gen Surg Hosp 1, Zhengzhou 450052, Peoples R China
|Lu, JF,Leng, XS,Peng, JR,et al. Induction of cytotoxic T lymphocytes from the peripheral blood of a hepatocellular carcinoma patient using melanoma antigen-1 (MAGE-1) peptide[J]. CHINESE MEDICAL JOURNAL,2002,115(7):1002-1005.|
|APA||Lu, JF.,Leng, XS.,Peng, JR.,Mou, DC.,Pang, XW.,...&Chen, WF.(2002).Induction of cytotoxic T lymphocytes from the peripheral blood of a hepatocellular carcinoma patient using melanoma antigen-1 (MAGE-1) peptide.CHINESE MEDICAL JOURNAL,115(7),1002-1005.|
|MLA||Lu, JF,et al."Induction of cytotoxic T lymphocytes from the peripheral blood of a hepatocellular carcinoma patient using melanoma antigen-1 (MAGE-1) peptide".CHINESE MEDICAL JOURNAL 115.7(2002):1002-1005.|