TY - JOUR
T1 - Intravenous and isolated limb perfusion delivery of wild type and a tumor-selective replicating mutant vaccinia virus in nonhuman primates
AU - Naik, Arpana M.
AU - Chalikonda, Sricharan
AU - McCart, J. Andrea
AU - Xu, Hui
AU - Guo, Z. Sheng
AU - Langham, Gregory
AU - Gardner, Donald
AU - Mocellin, Simone
AU - Lokshin, Anna E.
AU - Moss, Bernard
AU - Alexander, H. Richard
AU - Bartlett, David L.
PY - 2006/1
Y1 - 2006/1
N2 - In this study we examine the safety, feasibility, and biodistribution of a tumor-selective mutant vaccinia (vvDD) and wild-type WR (vF13) vaccinia after delivery via intradermal or intravenous infection or isolated limb perfusion (ILP) in rhesus macaques. By intradermal inoculation, 106 PFU of vvDD caused a minimal skin reaction whereas vF13 caused marked erythema and necrosis with a peak indurated area of 108 cm2. By intravenous delivery, vvDD caused no clinical symptoms of viremia and no viral recovery from tissues, serum, saliva, urine, or feces. In contrast, vF13 caused symptoms of lethargy, anorexia, fever, and signs of viremia. Delivery of vF13 via ILP resulted in numerous cutaneous pox lesions localized solely to the perfused limb with high viral recovery in the perfused skin and muscle. ILP with vvDD resulted in no visible pox lesions and no clinical signs or symptoms of viremia. No long-term toxicity was identified after ILP with 109 PFU of vvDD, and no virus was recovered from any tissue, serum, saliva, urine, or fecal sample. These results suggest that vvDD appears to be safe in primates, and thus vvDD should be further investigated for clinical trial in human cancer patients.
AB - In this study we examine the safety, feasibility, and biodistribution of a tumor-selective mutant vaccinia (vvDD) and wild-type WR (vF13) vaccinia after delivery via intradermal or intravenous infection or isolated limb perfusion (ILP) in rhesus macaques. By intradermal inoculation, 106 PFU of vvDD caused a minimal skin reaction whereas vF13 caused marked erythema and necrosis with a peak indurated area of 108 cm2. By intravenous delivery, vvDD caused no clinical symptoms of viremia and no viral recovery from tissues, serum, saliva, urine, or feces. In contrast, vF13 caused symptoms of lethargy, anorexia, fever, and signs of viremia. Delivery of vF13 via ILP resulted in numerous cutaneous pox lesions localized solely to the perfused limb with high viral recovery in the perfused skin and muscle. ILP with vvDD resulted in no visible pox lesions and no clinical signs or symptoms of viremia. No long-term toxicity was identified after ILP with 109 PFU of vvDD, and no virus was recovered from any tissue, serum, saliva, urine, or fecal sample. These results suggest that vvDD appears to be safe in primates, and thus vvDD should be further investigated for clinical trial in human cancer patients.
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U2 - 10.1089/hum.2006.17.31
DO - 10.1089/hum.2006.17.31
M3 - Article
C2 - 16409123
AN - SCOPUS:30744464395
SN - 1043-0342
VL - 17
SP - 31
EP - 45
JO - Human Gene Therapy
JF - Human Gene Therapy
IS - 1
ER -