TY - JOUR
T1 - Dendritic cells transduced with TAT protein transduction domain-containing tyrosinase-related protein 2 vaccinate against murine melanoma
AU - Shibagaki, Naotaka
AU - Udey, Mark C.
PY - 2003/4/1
Y1 - 2003/4/1
N2 - Incorporation of an 11 amino acid region of the HIV TAT protein transduction domain (TAT PTD) into proteins facilitates rapid, efficient entry into cells. We previously showed that rTAT-PTD-OVA-transduced dendritic cells (DC) stimulated antigen (Ag)-specific CTL and Th cells, and vaccinated against OVA-expressing tumors. Here we studied B16 melanoma in C57BL/6 mice, using murine tyrosinase-related protein 2 (Trp2) as a candidate tumor Ag. We produced a 472-amino acid N-terminal fragment of Trp2 protein (rTrp2Δ) with or without PTD. Although PTD-deficient rTrp2Δ was ineffective, mice given rTAT-PTD-Trp2Δ-transduced DC were efficiently primed for Trp2180-188 peptide-specific and B16-reactive CTL. In 58% of such mice, growth of melanomas was prevented. Trp2180-188 peptide-pulsed DC protected 35% of recipients, and irradiated GM-CSF-producing B16 cells protected 75%. rTAT-PTD-Trp2Δ-transduced DC induced a more vigorous memory response to B16 rechallenge than the other regimens, and protected 30% of recipients from progressive tumor development in treatment studies. In this setting, Trp2 peptide-treated DC protected 20% and irradiated GM-CSF-producing cells protected 0%. Both tumor prevention and tumor treatment were CD8+ T cell dependent. Vaccination with rTAT-PTD-Trp2Δ-transduced DC induced a robust CTL response and durable anti-melanoma immunity. This approach should be clinically applicable, and offers theoretical and practical advantages to those that are in current use.
AB - Incorporation of an 11 amino acid region of the HIV TAT protein transduction domain (TAT PTD) into proteins facilitates rapid, efficient entry into cells. We previously showed that rTAT-PTD-OVA-transduced dendritic cells (DC) stimulated antigen (Ag)-specific CTL and Th cells, and vaccinated against OVA-expressing tumors. Here we studied B16 melanoma in C57BL/6 mice, using murine tyrosinase-related protein 2 (Trp2) as a candidate tumor Ag. We produced a 472-amino acid N-terminal fragment of Trp2 protein (rTrp2Δ) with or without PTD. Although PTD-deficient rTrp2Δ was ineffective, mice given rTAT-PTD-Trp2Δ-transduced DC were efficiently primed for Trp2180-188 peptide-specific and B16-reactive CTL. In 58% of such mice, growth of melanomas was prevented. Trp2180-188 peptide-pulsed DC protected 35% of recipients, and irradiated GM-CSF-producing B16 cells protected 75%. rTAT-PTD-Trp2Δ-transduced DC induced a more vigorous memory response to B16 rechallenge than the other regimens, and protected 30% of recipients from progressive tumor development in treatment studies. In this setting, Trp2 peptide-treated DC protected 20% and irradiated GM-CSF-producing cells protected 0%. Both tumor prevention and tumor treatment were CD8+ T cell dependent. Vaccination with rTAT-PTD-Trp2Δ-transduced DC induced a robust CTL response and durable anti-melanoma immunity. This approach should be clinically applicable, and offers theoretical and practical advantages to those that are in current use.
KW - Cytotoxic lymphocyte
KW - Dendritic cell
KW - Melanoma
KW - Protein transduction
KW - Vaccination
UR - http://www.scopus.com/inward/record.url?scp=0038744609&partnerID=8YFLogxK
U2 - 10.1002/eji.200323709
DO - 10.1002/eji.200323709
M3 - Review article
C2 - 12672050
AN - SCOPUS:0038744609
SN - 0014-2980
VL - 33
SP - 850
EP - 860
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 4
ER -