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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Animals
-
CD8-Positive T-Lymphocytes / immunology*
-
Cancer Vaccines / immunology*
-
Cancer Vaccines / pharmacology
-
Carcinoma, Non-Small-Cell Lung / immunology
-
Carcinoma, Non-Small-Cell Lung / prevention & control
-
Carcinoma, Non-Small-Cell Lung / secondary
-
Female
-
Immunologic Memory / immunology*
-
Immunotherapy, Adoptive / methods
-
Interleukin-8 / biosynthesis
-
Interleukin-8 / genetics
-
Interleukin-8 / immunology*
-
Lung Neoplasms / immunology
-
Lung Neoplasms / prevention & control
-
Lung Neoplasms / secondary
-
Lymphocyte Activation / immunology
-
Mammary Neoplasms, Experimental / immunology*
-
Mammary Neoplasms, Experimental / pathology
-
Mammary Neoplasms, Experimental / therapy
-
Mice
-
Mice, Inbred BALB C
-
Mice, Inbred C57BL
-
Mice, SCID
-
Proto-Oncogene Proteins c-fos / biosynthesis
-
Proto-Oncogene Proteins c-fos / genetics
-
Proto-Oncogene Proteins c-fos / immunology*
-
T-Lymphocytes, Cytotoxic / immunology
-
Vaccines, DNA / immunology*
-
Vaccines, DNA / pharmacology
Substances
-
Cancer Vaccines
-
Interleukin-8
-
Proto-Oncogene Proteins c-fos
-
Vaccines, DNA
-
fos-related antigen 1