Combining Human and Rat Sequences in Her-2 DNA Vaccines Blunts Immune Tolerance and Drives Antitumor Immunity
| Autor: | Joyce D. Reyes, Amy Weise, Elena Quaglino, Olga Radkevich-Brown, Marie P. Piechocki, Richard F. Jones, Wei Zen Wei, Augusto Amici, Jennifer B. Jacob |
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| Rok vydání: | 2010 |
| Předmět: |
Cancer Research
Transgene Heterologous Mice Transgenic Biology Cancer Vaccines Article Immune tolerance DNA vaccination Mice Immune system Antigen Immune Tolerance Vaccines DNA Animals Humans Mice Inbred BALB C Mammary Neoplasms Experimental Genes erbB-2 Fusion protein Virology Rats Mice Inbred C57BL Oncology Female Cancer vaccine |
| Zdroj: | Cancer Research. 70:119-128 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-09-2554 |
| Popis: | 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/c × C57BL/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. Cancer Res; 70(1); 119–28 |
| Databáze: | OpenAIRE |
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