58Â° Congresso Nazionale SCIVAC: Oncologia veterinaria

More documents

Recommendations

Info

58° Congresso Nazionale SCIVAC • Milano, 7-9 Marzo 2008 • Oncologia veterinaria - Alle soglie del III Millennio SMALL MOLECULAR INHIBITOR THERAPY While a variety of pathways have been established as anticancer treatment targets, signaling molecules in the receptor tyroinse kinase class seem to be the closest to providing a window to clinical applicability. The promiscuous RTKI imatinib mesylate (Gleevec) has been used in cats and dogs with mast cell disease with some success. The dose in cats is 10 mg/kg daily, but remission in visceral mast cell disease may take several weeks to be detectable. In the dog, the dose used has ranged from 5 mg/kg to 10 mg/kg daily, with significant hepatobiliary toxicity noted in some instances. Until the underlying mechanism of this potentially lethal toxicity has been identified so that at risk cases can be screed, the drug should be used with extreme care and clear client informed consent of risk in canine patients. Investigational therapy with a different small molecular inhibitor of receptor tyrosine kinase signaling, (SU11654 - newly named Palladia by Pfizer), which acts as an inhibitor of c- KIT a variety of RTKs including c-Kit, PDGFR, and VEGF, has been carried out in the dog. Response has been seen in 11/22 dogs with MCT, as well as limited numbers of dogs with soft tissue sarcomas, mammary carcinomas, and multiple myelomas. The overall response rated noted with this drug was 28% (16/57 dogs) and those dogs with a receptor mutation were the ones most likely to respond. However, this product is not yet commercially available and remains in trials. Other small molecular pathway inhibitors are under investigation in the dog, with studies ongoing both in vitro and in vivo. This field of research is experiencing an explosive development phase in human oncology, with many pathways and molecules being explored as potential treatment targets. A large additional effort in funded clinical trials, and time for outcomes assessment, will tell which of these agents will prove most effective, safe, and practical for use in veterinary medicine in the future. ANTITUMOR VACCINES Long-term survival of dogs with advanced malignant melanoma was achieved after DNA vaccination with xenogeneic human tyrosinase antigen, available under limited license in the United States from Meriel. In this phase one trial, median survival for 9 dogs treated was 389 days, with complete responses reported and greater that 588-day survival for one dog with bulky non-resectable disease. Dogs that demonstrated antigen specific antibody responses were more likely to have positive responses clinically. Gene therapy has also been employed experimentally in dogs with malignant melanoma. Intratumoral administration of DNA encoding bacterial superantigen of staphy- 78
58° Congresso Nazionale SCIVAC • Milano, 7-9 Marzo 2008 • Oncologia veterinaria - Alle soglie del III Millennio lococcal enterotoxin B combined with either genes for GM-CSF or IL-2 resulted in an overall response rate of 46% in 26 dogs treated. Intratumoral infiltration with CD4+ and CD8+ T cells and macrophages was noted, as well as high levels of antitumor cytotoxic T lymphocyte activity in peripheral blood. Dendritic cell vaccines have also been attempted, using ex-vivo differentiated bone marrow or peripheral blood derived dendritic cells have been created by exposing blood or bone marrow mononuclear cells to differentiation conditions in cell culture. These dendritic cells are then loaded with antigens (cell extracts, nucleosome fragments from apoptotic bodies created in primary tumor culture) then used as active specific tumor vaccine therapy against melanoma. Address for correspondence: Barbara E. Kitchell Professor and Director, Center for Comparative Oncology Michigan State University College of Veterinary Medicine 79
Page 1:
58° Congresso Nazionale SCIVAC •
Page 5 and 6:
Page 9:
Page 12 and 13:
Page 14 and 15:
nr. 6312 Sedazione IL PASSATO È FI
Page 16 and 17:
Page 18 and 19:
Page 20 and 21:
Page 22 and 23:
Page 24 and 25:
Page 26 and 27:
Page 28 and 29: 58° Congresso Nazionale SCIVAC •
Page 128 and 129:
Page 130 and 131:
Page 132 and 133:
Page 134 and 135:
Page 136 and 137:
Page 138 and 139:
Page 140 and 141:
Page 142 and 143:
Page 144 and 145:
Page 146 and 147:
Page 148 and 149:
Page 150 and 151:
Page 152 and 153:
Page 154 and 155:
Page 156 and 157:
Page 158 and 159:
Page 160 and 161:
Page 162 and 163:
Page 165 and 166:
POSTER Gli estratti sono elencati i
Page 167 and 168:
Page 169 and 170:
Page 171 and 172:
Page 173 and 174:
Page 175 and 176:
Page 177 and 178:
Page 179 and 180:
Page 181 and 182:
Page 183 and 184:
Page 185 and 186:
Page 187 and 188:
Page 189 and 190:
Page 191 and 192:
show all

58Â° Congresso Nazionale SCIVAC: Oncologia veterinaria

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?