Corey Smith and Larry Lomax, LSUSVM Pathobiological Sciences

Tumor Cell Necrosis and Tumor Angiogenesis Inhibition as an Indication of the Effectiveness of an Antiangiogenesis Vaccination in a Rodent Model of Breast Carcinoma

Angiogenesis is required for tumors to grow beyond the size of 1 mm. Tumors secrete vascular endothelial growth factor (VEGF) to induce angiogenesis. Antiangiogenic therapy is a promising area of cancer treatment. A vaccine made by the Mastology Research Institute aims to have the body produce antibodies against VEGF. The efficacy of this vaccine was examined in two experiments (I and II) in a Fisher 344 rat mammary cancer model. After the rats had been vaccinated they were injected with 1 X 106 13762 Mat B III rat mammary adenocarcinoma cells (ATCC). After being sacrificed the tumors were taken for histological analysis. Using the percent of necrotic area versus total tumor area and the number of vessels per “hot spot”, the effectiveness of the vaccine against angiogenesis was determined. The results showed that for experiment I the percent of tumor cell necrosis was: control had 20.2% necrosis, vaccine plus Incomplete Freund’s (IF) had 38.4% necrosis, and vaccine without IF had 42.1% necrosis. The percents of tumor cell necrosis for experiment II were: the control had 18.6% necrosis, vaccine with antigen attached to Bovine Serum Albumin (BSA) and IF had 29% necrosis, and the vaccine with IF had 39.4% necrosis. For experiment I the results for the vessel count per hot spot were: control 14.7, vaccine plus IF 8.6, and vaccine without IF 7.7. The results for experiment II were: control 13.6, vaccine with antigen attached to BSA and IF 7.7, and vaccine with IF 6.3 mean number of vessels per hot spot. For both experiments there was significant difference between the control and the two treatment groups for both percent necrosis and mean number of vessels per hot spot. Animals that were vaccinated had an increase in percent of tumor cell necrosis and a decrease in the number of blood vessels in the mammary tumor. These studies demonstrate the effectiveness of the vaccine in retarding angiogenesis in the rodent mammary tumor and thereby causing more tumor cell necrosis as compared to controls. There were no significant differences between the different vaccine groups.