Font Size: a A A

The Study Of Melanoma-associated Antigen Geen And The Adoptive Cellular Immunotherapy On Breast Cancer With The Dendritic Cells Loaded With Its Peptide

Posted on:2006-08-02Degree:DoctorType:Dissertation
Country:ChinaCandidate:Q MaFull Text:PDF
GTID:1104360152994775Subject:Department of General Surgery
Abstract/Summary:PDF Full Text Request
Background:Since van der Bruggen found the first melanoma-associated antigen gene (Mage) and its peptide MZ2-E in 1991, the researchers had found dozens of Mage in many different types of tumors. They were all mapped to chromosome X and shared certain homologous regions. They were all the members of Mage family, including six subgroups A, B, C, D, E, F. And the subgroups A, B. C shared certain homology. They has been found in many different types of malignant tumors, but not in normal adult tissues except the testis and placenta. Though scientists didin't know the physiological function of Mage genes encoding proteins, researchers had found that they were tumor antigens which could be recognized by specific T cells in malignant tumor. It suggeated us Mage maybe a novel marker to detect tumor and its peptide may be the most promising candidate for tumor-specific immunotherapy of cancer.Dendritic cells (DCs) were the most potent and the only antigen presenting cells (APC), which were capable of activating naive T cells and initiating primary immune response. Recently, more and more evidence showed that the cellular immunity induced by dendritic cells, especial theCTL response, played an important role in the immune response against the malignant tumor. The adoptive cellular immunotherapy based on the dendritic cells loaded with antigen is becoming the highlight in the biology therpy of malignant tumor.The expression of Mage-A1 , A2, A3 in breast cancer tissues and four breast cancer cell lines was researched. Their mRNA was used as the marker to detecte the occult tumor cells in peripheral blood of patients with breast cancer. The experimental immunotherapy based on dendritic cells loaded with Mage-A3 peptide were studied on the mice model of breast cancer. 1. Expression of Mage-A1, A2, A3 in breast cancer tissue and breast cancer cell linesObjectives To study the expression of Mage-A1, A2, A3 in breast cancer tissues and four breast cancer cell lines.Methods The expression of Mage-A1, A2, A3 in breast cancer tissues and four breast cancer cell lines, MCF-7, Sk-Br-3, MDA-MB-435s and TM40D was detected by reverse transcription polymerase chain reaction (RT-PCR) . Results The positive expression rate of Mage-A in breast cancer tissues was 13/33 (39%) , of Mage-Al was 4/33 (12%) , of Mage-A2 was 8/33 ( 24%), and of Mage-A3 was 7/33( 21%), respectively. Both Mage-A1 and Mage-A3 were positive in breast cancer cell lines MCF-7 and Sk-Br-3. MDA-MB-435s expressed Mage-A2 and Mage-A3. Mage-A3 was positive in TM40D.Conclusions Mage genes were often expressed in breast cancer, butexpression of Mages varied in the breast cancer cell lines. Mage geneencoding proteins are eligible for Mage-peptide-based activeimmunotherapy.2. Expression of Mage-A1, A2, A3 in the occult tumor cells in theperipheral blood of patients with breast cancerObjective To detect tumor cells in the peripheral blood of patients withbreast cancer by using the mRNA of the Mage-A1 and Mage-A3 genes asspecific tumor markers.Methods Peripheral blood was obtained from 40 breast cancer patients and20 patients with benign diseases. The mRNA of the Mage-A1 and Mage-A3genes in the peripheral blood mononuclear cells (PBMCs) was detected bynested RT-PCR. The Mage-A1 and Mage-A3 transcripts in the tumor tissuesof these breast cancer patients were also detected by RT-PCR.Results Of the 40 breast cancer patients, Mage-Al and Mage-A3 mRNAwere positive in 12.5% ( 5/40) and 17.5% ( 7/40 ) of PBMCs respectively, andin 15 % ( 6/40 ) and 22.5 % ( 9/ 40 ) of breast cancer tissues respectively. Inthe PBMCs of the 40 breast cancer patients, 10( 25 % )samples were detectedto express at least one type of Mage mRNA. Mage mRNA were not found inthe PBMCs from the patients whose tumors did not express the Mage genes,nor in the PBMCs from the 20 patients with benign diseases. The positiverate of Mage mRNA in the PBMCs was closely correlated with the TNMstages.Conclusion Mage-A1 and Mage-A3 mRNA could be specificallydetected in the PBMCs of breast cancer pati...
Keywords/Search Tags:melanoma-associated antigen gene, Mage, breast neoplasms, dendritic cells, adoptive cellular immunotherapy, cytotoxic T lymphocyte
PDF Full Text Request
Related items