A DNA vaccine targeting Fos-related antigen 1 enhanced by IL-18 induces long-lived T-cell memory against tumor recurrence

作者：Luo YP; Zhou H; Mizutani M; Mizutani N; Liu C; Xiang R; Reisfeld RA^*

来源：Cancer Research, 2005, 65(8): 3419-3427.

DOI：10.1158/0008-5472.can-04-3120

A novel vaccination strategy induced specific CW8(+) 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.

• 出版日期2005-4-15