| First Author | Jacob JB | Year | 2010 |
| Journal | Cancer Res | Volume | 70 |
| Issue | 1 | Pages | 119-28 |
| PubMed ID | 20048073 | Mgi Jnum | J:155732 |
| Mgi Id | MGI:4415625 | Doi | 10.1158/0008-5472.CAN-09-2554 |
| Citation | Jacob JB, et al. (2010) Combining human and rat sequences in her-2 DNA vaccines blunts immune tolerance and drives antitumor immunity. Cancer Res 70(1):119-28 |
| abstractText | Immune tolerance to tumor-associated self-antigens poses a major challenge in the ability to mount an effective cancer vaccine response. To overcome immune tolerance to HER-2, we formulated DNA vaccines that express both human HER-2 and heterologous rat Neu sequences in separate plasmids or as single hybrid constructs that encode HER-2/Neu fusion proteins. Candidate vaccines were tested in Her-2 transgenic (Tg) mice of BALB/c (BALB), BALB/cxC57BL/6 F1 (F1), or C57BL/6 (B6) background, which exhibit decreasing immune responsiveness to HER-2. Analysis of various cocktails or hybrid vaccines defined a requirement for particular combination of HER/2/Neu sequences to effectively prime immune effector cells in HER-2 Tg mice. In B6 HER-2 Tg mice, rejection of HER-2-positive tumors protected mice from HER-2-negative tumors, providing evidence of epitope spreading. Our findings show that a strategy of combining heterologous antigen with self-antigens could produce a potent DNA vaccine that may be applicable to other tumor-associated antigens. |
