Use of an Extracellular Matrix Material as a Vaccine Carrier and Adjuvant

Abstract

Background: The addition of adjuvants frequently enhances the efficacy of vaccine preparations. Interest in the use of vaccines as a means to treat cancer has led to the search for improved adjuvants. Because cancer vaccines based on whole cell preparations might benefit from an adjuvant which enhances expression of antigens expressed during tumor cell growth, we evaluated the utility of an extracellular matrix material, porcine small intestinal submucosa (SIS), as a cancer vaccine adjuvant. Materials and Methods: After tumors were produced in Lobund-Wistar (LW) rats by subcutaneous administration of PAIII prostate adenocarcinoma cells, rats underwent surgical debulking of the tumor mass. Groups of ten rats were then vaccinated directly on the tumor bed with glutaraldehyde-treated tumor (GFT) cells harvested from a PAIII tumor; a 2×2 cm section of glutaraldehyde-treated SIS; or a 2×2 cm section of SIS on which harvested tumor cells were grown for either 3 days (GFT-S3) or 28 days (GFT-S28) and then treated with glutaraldehyde. In addition, a group was left untreated after debulking. Results: When tumors and lungs were harvested 21 days later, there were no significant differences between mean tumor weights of rats vaccinated with GFT cells or SIS and those which were left untreated. In contrast, rats vaccinated with GFT-S3 had a significant (p<0.01) reduction of greater than 65% and 58% in mean tumor weight compared to untreated rats and GFT cell-vaccinated rats, respectively. GFT-S28 rats had a significant (p<0.05) reduction of 59% and 49% compared to untreated rats and GFT cell-vaccinated rats, respectively. There was no significant difference in mean tumor weight between GFT-S3 and GFT-S28 rats. Furthermore, while most untreated rats had at least one metastatic focus in the lungs, a reduction was seen in rats vaccinated with GFT (7/10 positive), GFT-S3 (2/5 positive) and GFT-S28 (2/5 positive) cells. Conclusion: SIS enhanced the efficacy of a tissue vaccine for prostate cancer, demonstrating the potential utility of extracellular matrices as novel vaccine adjuvants.