TY - JOUR
T1 - A tat fusion protein-based tumor vaccine for breast cancer
AU - Viehl, Carsten T.
AU - Becker-Hapak, Michelle
AU - Lewis, Jason S.
AU - Tanaka, Yoshiyuki
AU - Liyanage, Udaya K.
AU - Linehan, David C.
AU - Eberlein, Timothy J.
AU - Goedegebuure, Peter S.
N1 - Funding Information:
The authors thank Dr. S. F. Dowdy, San Diego, CA, for providing the Tat-H A vector; Dr. E. M. Jaffee, Baltimore, MD, for the NT5 cell line; Dr. R. J. Bat-tafarano, St. Louis, MO, for the third ESO cell line; and Todd T. Moore for invaluable technical assistance. Supported in part by grants from the Swiss National Science Foundation (81BE-067988) and the Regional Cancer League of Basel, Switzerland (to C.T.V.). PET imaging was supported by a National Institutes of Health/National Cancer Institute Small Animal Imaging Research Program (SAIRP) grant (R24 CA083060), with additional support from the Small Animal Imaging Core (SAIC) of the Alvin J. Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital, St. Louis, MO. The SAIC is supported by National Cancer Institute Cancer Center Support Grant 1 P30 CA091842.
PY - 2005/7
Y1 - 2005/7
N2 - 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 γ 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.
AB - 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 γ 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.
KW - Animal study
KW - Breast cancer
KW - Cancer vaccine
KW - Her2/neu
KW - Tat fusion protein
UR - http://www.scopus.com/inward/record.url?scp=21244434878&partnerID=8YFLogxK
U2 - 10.1245/ASO.2005.06.028
DO - 10.1245/ASO.2005.06.028
M3 - Article
C2 - 15889213
AN - SCOPUS:21244434878
SN - 1068-9265
VL - 12
SP - 517
EP - 525
JO - Annals of Surgical Oncology
JF - Annals of Surgical Oncology
IS - 7
ER -