A DNA vaccine targeting Fos-related antigen 1 enhanced by IL-18 induces long-lived T-cell memory against tumor recurrence.
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.
Luo
Yunping
Y
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA.
Zhou
He
H
Mizutani
Masato
M
Mizutani
Noriko
N
Liu
Cheng
C
Xiang
Rong
R
Reisfeld
Ralph A
RA
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology* / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000517:prevention & control / Q000556:secondary; D005260:Female; D007156:Immunologic Memory / Q000276:immunology*; D016219:Immunotherapy, Adoptive / Q000379:methods; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000556:secondary; D008213:Lymphocyte Activation / Q000276:immunology; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology* / Q000494:pharmacology; D000099169:Fos-Related Antigen 1
D019496:Cancer Vaccines; D016209:Interleukin-8; D016760:Proto-Oncogene Proteins c-fos; D019444:Vaccines, DNA; D000099169:Fos-Related Antigen 1