A tat fusion protein-based tumor vaccine for breast cancer.
BACKGROUND
We recently reported that dendritic cells (DCs) transduced with a fusion protein between Her2/neu and the protein transduction domain Tat (DC-Tat-extracellular domain [ECD]) induced Her2/neu-specific CD8(+) T cells in vitro. This study tested the in vivo efficacy of DC-Tat-ECD in a murine breast cancer model.


METHODS
FVB/N mice received one or two weekly intraperitoneal immunizations with syngeneic DC-Tat-ECD followed by a tumor challenge with syngeneic neu(+) breast cancer cells, and tumor development was monitored. To test for Her2/neu specificity, CD4(+) and CD8(+) cells were isolated through magnetic bead separation and analyzed for specific interferon gamma release.


RESULTS
Intraperitoneally injected DCs migrated to secondary lymphoid organs, as evidenced by small-animal positron emission tomography studies. Immunized mice developed palpable tumors significantly later than control mice injected with DC-Tat-empty (P = .001 and P < .05 for two immunizations and for one immunization, respectively) or mice that received no DCs (P = .001 and P < .05). Similarly, immunized mice had smaller resulting tumors than mice injected with DC-Tat-empty (P < .05 and P < .01) or untreated mice (P < .001 and P < .001). Significantly more tumor-specific CD8(+) splenocytes were found in twice-immunized mice than in untreated animals (P < .001). Similarly, a T-helper type 1 CD4(+) T-cell response was observed.


CONCLUSIONS
Protein-transduced DCs may be effective vaccines for the treatment of cancer.
Viehl
Carsten T
CT
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Becker-Hapak
Michelle
M
Lewis
Jason S
JS
Tanaka
Yoshiyuki
Y
Liyanage
Udaya K
UK
Linehan
David C
DC
Eberlein
Timothy J
TJ
Goedegebuure
Peter S
PS
D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D019496:Cancer Vaccines / Q000276:immunology* / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D015696:Gene Products, tat / Q000276:immunology*; D008325:Mammary Neoplasms, Experimental; D051379:Mice; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology*
D019496:Cancer Vaccines; D015696:Gene Products, tat; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins