Development of tumor-specific DNA vaccines eradicating metastatic lesions

虽然黑色素瘤主要影响皮肤，但它以容易发生转移而臭名昭著。转移性黑色素瘤对多种治疗方法高度耐药。我们用含有未甲基化CpG基序的合成寡核苷酸(ODN)检测了瘤周单一治疗对小鼠皮肤B16F10黑色素瘤的抗转移潜能。我们证明，重复瘤周注射CpG ODN可以显著减小皮肤肿瘤的大小。瘤周CpG ODN治疗皮肤肿瘤阻止了肺B16F10集落的发展。过继转移来自CpG ODN处理的小鼠的脾细胞显著减少了受体幼小鼠先前建立的肺集落数量。T淋巴细胞耗竭研究表明，抗转移作用依赖于CD8+T细胞和CD4+T细胞。这些结果表明，CpG ODN有望作为一种预防和治疗黑色素瘤的抗转移措施。

Although melanoma mostly affects the skin, it is notorious for its propensity to easily develop metastasis. Metastatic melanoma is highly resistant to a variety of therapies. We examined the anti-metastatic potential of peritumoral monotherapy against murine cutaneous B16F10 melanoma with synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs. We demonstrated that repeated peritumoral injections of CpG ODNs significantly reduced skin tumor size. Peritumoral CpG ODN-treatment of skin tumors prevented the development of pulmonary B16F10 colonies. Adoptive transfer of splenocytes obtained from CpG ODN-treated mice markedly reduced the number of previously established pulmonary colonies in recipient naive mice. T-lymphocyte depletion studies indicated that the anti-metastatic effect was dependent on both CD4^+ and CD8^+ T cells. These results suggest that CpG ODNs are promising as a preventive and therapeutic anti-metastatic measure against melanoma.