Abstract
A novel vaccination strategy induced specific CD8+ T cell–mediated immunity that eradicated spontaneous and experimental pulmonary cancer metastases in syngeneic mice and was also effective in a therapeutic setting of established breast cancer metastases. This was achieved by targeting transcription factor Fos-related antigen 1(Fra-1), overexpressed by many tumor cells, with an ubiquitinated DNA vaccine against Fra-1, coexpressing secretory IL-18. Insight into the immunologic mechanisms involved was provided by adoptive transfer of T lymphocytes from successfully immunized BALB/c mice to syngeneic severe combined immunodeficient (SCID) mice. Specifically, long-lived T memory cells were maintained dormant in nonlymphoid tissues by IL-18 in the absence of tumor antigen. Importantly, a second tumor cell challenge of these SCID mice restored both, robust tumor-specific cytotoxicity and long-lived T-cell memory, capable of eradicating established pulmonary cancer metastases, suggesting that this vaccine could be effective against tumor recurrence.
- DNA vaccine
- Fra-1
- T cell memory
- Interleukin 18
- Nonlymphoid tissue
Footnotes
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Note: This is the Scripps Research Institute's article number 16316-IMM.
- Received August 30, 2004.
- Revision received December 30, 2004.
- Accepted February 10, 2005.
- ©2005 American Association for Cancer Research.
Volume 65, Issue 8
