TITLE

Tumor-specific immunity in MUC1.Tg mice induced by immunization with peptide vaccines from the cytoplasmic tail of CD227 (MUC1)

AUTHOR(S)
Kohlgraf, Karl G.; Gawron, Andrew J.; Higashi, Michiyo; VanLith, Michelle L.; XiaoLing Shen; Caffrey, Thomas C.; Anderson, Judy M.; Hollingsworth, Michael A.
PUB. DATE
December 2004
SOURCE
Cancer Immunology, Immunotherapy;Dec2004, Vol. 53 Issue 12, p1068
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Purpose: CD227 (MUC1), a membrane-associated glycoprotein expressed by many types of ductal epithelia, including pancreas, breast, lung, and gastrointestinal tract, is overexpressed and aberrantly glycosylated by malignant cells. We sought to define epitopes on MUC1 recognized by the different cell-mediated immune responses by an in vivo assay. Epitopes identified by this assay were evaluated for efficacy to protect mice transgenic for human MUC1 (MUC1.Tg) against MUC1-expressing tumor growth. Methods: We investigated contributions of the tandem repeat (TR) and the cytoplasmic tail (CT) of MUC1 to the MUC1-specific immunological rejection of tumor cells. MUC1 cDNA constructs, in which the TR region was deleted or the CT was truncated, were transfected into two different murine tumor cell lines (B16 and Panc02), which were used to challenge mice and evaluate immunological rejection of the tumors. We used tumor rejection in vivo to define epitopes on the TR and CT of MUC1 recognized by T cell-mediated immune responses in a preclinical murine model. Results: Our findings demonstrated that the TR and a portion of the MUC1 CT contributed to CD4+ T cell rejection of MUC1-expressing B16 tumor cells, but not rejection of MUC1-expressing Panc02 tumor cells. A separate epitope in the CT of MUC1 was necessary for CD8+ T cell rejection of Panc02 tumor cells. Based on these studies, we sought to evaluate the efficacy of immunizing mice transgenic for (and immunologically tolerant to) human MUC1 with peptides derived from the amino acid sequence of the CT of MUC1. Results showed that survival can be significantly prolonged in vaccinated MUC1.Tg mice challenged with MUC1-expressing tumor cells, without induction of autoimmune responses. Conclusions: These studies demonstrated that MUC1 peptides may be utilized as an effective anticancer immunotherapeutic, and confirmed the importance of immunogenic epitopes outside of the TR.
ACCESSION #
15397902

 

Related Articles

  • WSX1 Expression in Tumors Induces Immune Tolerance via Suppression of Effector Immune Cells. Dibra, Denada; Cutrera, Jeffry; Xueqing Xia; Shulin Li // PLoS ONE;2011, Vol. 6 Issue 4, p1 

    Crosstalk between tumor cells and the cognate microenvironment plays a crucial role in tumor initiation and progression. However, only a few genes are known to affect such a crosstalk. This study reveals that WSX1 plays such a role when highly expressed in tumor cells. The expression of WSX1 in...

  • Molecular modes of action of cephalotaxine and homoharringtonine from the coniferous tree Cephalotaxus hainanensis in human tumor cell lines. Efferth, Thomas; Sauerbrey, Axel; Halatsch, Marc-Eric; Ross, Douglas D.; Gebhart, Erich // Naunyn-Schmiedeberg's Archives of Pharmacology;Jan2003, Vol. 367 Issue 1, p56 

    Homoharringtonine (HHT) is an ester of cephalotaxine (CET), both of which derive from the Chinese coniferous tree Cephalotaxus hainanensis. HHT inhibited tumor cell growth at molar ranges comparable to established cytostatic drugs, whereas CET was 3–4 orders of magnitude less active....

  • Enhanced oncolysis by a tropism-modified telomerase-specific replication-selective adenoviral agent OBP-405 (‘Telomelysin-RGD’). Taki, Masaki; Kagawa, Shunsuke; Nishizaki, Masahiko; Mizuguchi, Hiroyuki; Hayakawa, Takao; Kyo, Satoru; Nagai, Katsuyuki; Urata, Yasuo; Tanaka, Noriaki; Fujiwara, Toshiyoshi // Oncogene;4/28/2005, Vol. 24 Issue 19, p3130 

    Replication-competent oncolytic viruses are being developed for human cancer therapy. We previously reported that an attenuated adenovirus (OBP-301,‘Telomelysin’), in which the hTERT promoter element drives expression of E1A and E1B genes linked with an IRES, could replicate in...

  • HE4 (WFDC2) Promotes Tumor Growth in Endometrial Cancer Cell Lines. Jinping Li; Haibin Chen; Mariani, Andrea; Dong Chen; Klatt, Edward; Podratz, Karl; Drapkin, Ronny; Broaddus, Russell; Dowdy, Sean; Shi-Wen Jiang // International Journal of Molecular Sciences;Mar2013, Vol. 14 Issue 3, p6026 

    HE4, also known as WFDC2, is a useful biomarker for ovarian cancer when either used alone or in combination with CA125. HE4 is also overexpressed in endometrial cancer (EC), but its function in cancer cells is not clear. In this study, we investigate the role of HE4 in EC progression. An...

  • Synthesis and Chemical Characterization of N10-Substituted Acridones as Reversers of Multidrug Resistance in Cancer Cells. Mayur, Y. C.; Gouda, Manjunath; Gopinath, Vadiraj S.; Shanta Kumar, S. M.; Prasad, V. V. S. Rajendra // Letters in Drug Design & Discovery;Jul2007, Vol. 4 Issue 5, p327 

    Synthesis of different N10-substituted-4-methyl acridones are described. The compounds are prepared with varying alkyl side chain length with propyl and butyl substitution and a tertiary amine group at the terminal end of the alkyl side chain. The structural requirement of in-vitro anti-cancer...

  • Clusterin confers gmcitabine resistance in pancreatic cancer. Qingfeng Chen; Zhengkun Wang; Kejun Zhang; Xiaoyi Liu; Weihong Cao; Lei Zhang; Shuhua Zhang; Bomin Yan; Yaoguang Wang; Chunping Xia // World Journal of Surgical Oncology;2011, Vol. 9 Issue 1, p59 

    Objective: To measure clusterin expression in pancreatic cancer tissues and cell lines and to evaluate whether clusterin confers resistance to gmcitabine in pancreatic cancer cells. Methods: Immunohistochemistry for clusterin was performed on 50 primary pancreatic cancer tissues and 25 matched...

  • P-0024 EXPRESSION AND FUNCTION OF METASTASIS-ASSOCIATED C4.4A IN HEPATOCELLULAR CARCINOMA. Magdalena, Görtz; Uwe, Galli; Peter, Schemmer // Annals of Oncology;Jun2014, Vol. 25 Issue suppl_2, pii20 

    No abstract available.

  • PROTECTIVE EFFECT OF MUC2 siRNA AGAINST COLON CANCER GROWTH THROUGH THE INDUCTION OF APOPTOSIS. Abaseri, Taghreed El; Foster, Jason // Egyptian Journal of Biochemistry & Molecular Biology;Jun2013, Vol. 31 Issue 1, p85 

    Mucinous colorectal cancers are highly aggressive phenotype presenting with more advanced disease and a poor prognosis. The biological mechanisms involved are unclear, but appear to be linked to mucin glycoprotein overexpression like MUC2. While the role of MUC2 in colon cancer metastasis is...

  • The miRNA-17∼92 cluster mediates chemoresistance and enhances tumor growth in mantle cell lymphoma via PI3K/AKT pathway activation. Rao, E; Jiang, C; Ji, M; Huang, X; Iqbal, J; Lenz, G; Wright, G; Staudt, L M; Zhao, Y; McKeithan, T W; Chan, W C; Fu, K // Leukemia (08876924);May2012, Vol. 26 Issue 5, p1064 

    The median survival of patients with mantle cell lymphoma (MCL) ranges from 3 to 5 years with current chemotherapeutic regimens. A common secondary genomic alteration detected in MCL is chromosome 13q31-q32 gain/amplification, which targets a microRNA (miRNA) cluster, miR-17∼92. On the...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics