Suckow Mark A, Hall Paul, Wolter William, Sailes Valerie, Hiles Michael C
Freimann Life Science Center, University of Notre Dame, Notre Dame, IN 46556, USA.
Anticancer Res. 2008 Sep-Oct;28(5A):2529-34.
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.
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 x 2 cm section of glutaraldehyde-treated SIS; or a 2 x 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.
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.
SIS enhanced the efficacy of a tissue vaccine for prostate cancer, demonstrating the potential utility of extracellular matrices as novel vaccine adjuvants.
添加佐剂常常能提高疫苗制剂的效力。将疫苗用作治疗癌症手段的兴趣促使人们寻找改良的佐剂。由于基于全细胞制剂的癌症疫苗可能会受益于一种能增强肿瘤细胞生长过程中表达的抗原表达的佐剂，我们评估了一种细胞外基质材料——猪小肠黏膜下层（SIS）作为癌症疫苗佐剂的效用。
通过皮下注射PAIII前列腺腺癌细胞在洛本德-威斯塔（LW）大鼠体内诱发肿瘤后，大鼠接受肿瘤块的手术减瘤。然后将十只大鼠分为一组，直接在肿瘤床上接种从PAIII肿瘤收获的经戊二醛处理的肿瘤（GFT）细胞；一块2×2厘米的经戊二醛处理的SIS；或一块2×2厘米的SIS，在其上接种收获的肿瘤细胞培养3天（GFT-S3）或28天（GFT-S28），然后用戊二醛处理。此外，一组大鼠在减瘤后不做处理。
21天后收获肿瘤和肺时，接种GFT细胞或SIS的大鼠的平均肿瘤重量与未处理大鼠之间没有显著差异。相比之下，接种GFT-S3的大鼠的平均肿瘤重量分别比未处理大鼠和接种GFT细胞的大鼠显著降低（p<0.0l）超过65%和58%。接种GFT-S28的大鼠的平均肿瘤重量分别比未处理大鼠和接种GFT细胞的大鼠显著降低（p<0.05）59%和49%。GFT-S3和GFT-S28大鼠的平均肿瘤重量没有显著差异。此外，虽然大多数未处理大鼠的肺部至少有一个转移灶，但接种GFT（7/10呈阳性）、GFT-S3（2/5呈阳性）和GFT-S28（2/5呈阳性）细胞的大鼠转移灶有所减少。
SIS提高了前列腺癌组织疫苗的效力，证明了细胞外基质作为新型疫苗佐剂的潜在效用。
