Chicken HSP70 DNA xenogeneic vaccine vaccine inhibits tumor growth in a canine cancer

• Main Authors: WenYing Yu, 游文瑛
• Other Authors: Rea-Min Chu
• Format: Others
• Language: en_US
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/46037135640381178106

碩士 === 國立臺灣大學 === 獸醫學研究所 === 98 === Immunization with xenogeneic DNA is a promising cancer treatment, as it generates autoantibodies and cytotoxic T cells to break the tumor tolerance against self-antigens. Heat shock protein 70 (HSP70) is overexpressed in many kinds of tumors and is believed to be heavily involved in tumor progression. This study employed a xenogeneic chicken HSP70 (chHSP70) DNA vaccine in a canine transmissible venereal tumor (CTVT) model in beagles to break the tumor tolerance by inducing immune responses towards canine HSP70 self-antigens. In this study, three vaccination groups were created: the first (G1) was designed to evaluate the prophylactic efficiency of the chHSP70 DNA vaccine by delivering the vaccine prior to tumor inoculation; the second (G2) was designed to evaluate the therapeutic efficacy in developed tumors by vaccinating the dogs after tumor inoculation; and the third (G3) consisted of the same vaccination schedule as that of G1, with the exception that the intramuscular injection/electroporation method used to administer the third vaccination in G1 was replaced with a transdermal injection. Four CTVT-bearing dogs that received no treatment (NT) served as controls, and one dog in each vaccination group immunized with empty vector served as a vector control. Tumor growth was notably inhibited only in the G1 dogs, in which the vaccination program triggered tumor regression much sooner (beginning in week 9) than in the G2 (week 18), G3 (week 12) and NT (week 14) dogs. The CD4+ subpopulation of tumor-infiltrating lymphocytes was significantly increased during tumor regression in the G1 dogs as compared with the G2 and NT dogs (56.77% vs. 23.56% and 22.73%, respectively) and was similar to that of G3. The tumor-specific cytotoxicity of peripheral blood mononuclear cells (PBMCs) in all dogs in the three vaccination groups was dramatically enhanced, and ELISpot assay indicated that canine HSP70-specific IFN-