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Publication : CD4+ T cell-mediated antigen-specific immunotherapy in a mouse model of cervical cancer.

First Author  Daniel D Year  2005
Journal  Cancer Res Volume  65
Issue  5 Pages  2018-25
PubMed ID  15753402 Mgi Jnum  J:97006
Mgi Id  MGI:3574140 Doi  10.1158/0008-5472.CAN-04-3444
Citation  Daniel D, et al. (2005) CD4+ T cell-mediated antigen-specific immunotherapy in a mouse model of cervical cancer. Cancer Res 65(5):2018-25
abstractText  A major agenda for tumor immunology is the generation of specific immune responses leading to the destruction of incipient and frank neoplasia. In this report, we show that a novel HPV16 E7 fusion protein can produce objective therapeutic responses against incipient cervical cancer in genetically engineered mice that express in the cervix the HPV16 early region genes implicated as causative agents in human cervical cancer. Although nonresponsive toward the HPV16 E7 oncoprotein in the CD8+ T-cell compartment by virtue of MHC haplotype, the mice were capable of mounting an induced CD4+ T-cell response against E7, and in addition developed spontaneous anti-E7 antibodies. HPV16/CD4-/- mice showed increased tumor burden indicative of CD4-mediated immune surveillance. Seeking to enhance the CD4 response, we immunized mice bearing incipient cervical cancer with a recombinant protein fusing E7 with a mycobacterial heat shock protein. The incidences of cervical carcinoma and of high-grade dysplasia (CIN 3) were consequently reduced by comparison to control mice. Thus, an HPV16 E7 immunogen holds promise for noninvasive treatment and prevention of human cervical cancer.
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