Ashour Abdel-Kader, Petersen Jason L, McIlhaney Mary M, Vose Julie M, Solheim Joyce C
Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA.
Hybridoma (Larchmt). 2006 Oct;25(5):306-8. doi: 10.1089/hyb.2006.25.306.
Patient idiotype-specific vaccines for treatment of non-Hodgkin's lymphoma have shown promise in clinical trials, encouraging efforts to enhance the effectiveness of idiotype vaccines further. It has previously been found that for some other types of experimental vaccines, the addition of transduction domains has improved vaccine immunogenicity. Transduction domains are short amino acid sequences that are capable of increasing transport through cellular membranes. In this study, we tested murine B cell 38C13 lymphoma idiotype DNA vaccines with human immunodeficiency virus (HIV) Tat-derived transduction sequences for efficacy against 38C13 challenge. The rate of tumor onset was similar for the idiotype and transduction domain-conjugated idiotype vaccine groups. At days 22-23 postchallenge, the number of surviving mice was significantly higher in the group that had received a DNA vaccine consisting of the 38C13 idiotype sequence plus modified Tat transduction sequence, in comparison with the group that received idiotype-only vaccines. Although the overall survival difference was not statistically significant following day 24, a trend toward an increased survival rate for mice receiving idiotype plus Tat-derived transduction domains was maintained through day 106 postchallenge. Thus, the addition to idiotype vaccines of specific sequences that facilitate intracellular transport may have potential to improve the effectiveness of such vaccines.
用于治疗非霍奇金淋巴瘤的患者独特型特异性疫苗在临床试验中已显示出前景，这鼓励了进一步提高独特型疫苗有效性的努力。此前已发现，对于某些其他类型的实验性疫苗，添加转导结构域可提高疫苗的免疫原性。转导结构域是能够增加通过细胞膜转运的短氨基酸序列。在本研究中，我们测试了带有源自人类免疫缺陷病毒（HIV）Tat的转导序列的鼠B细胞38C13淋巴瘤独特型DNA疫苗对38C13攻击的疗效。独特型疫苗组和转导结构域偶联独特型疫苗组的肿瘤发病速率相似。在攻击后第22 - 23天，与仅接受独特型疫苗的组相比，接受由38C13独特型序列加修饰的Tat转导序列组成的DNA疫苗的组中存活小鼠的数量显著更高。尽管在第24天之后总体生存差异无统计学意义，但在攻击后第106天，接受独特型加Tat衍生转导结构域的小鼠的存活率仍保持上升趋势。因此，在独特型疫苗中添加有助于细胞内转运的特定序列可能有潜力提高此类疫苗的有效性。
