Transgenic expression of human gp100 and RANTES at specific time points for suppression of melanoma

The induction of strong cell-mediated immunity against targeted cancer cells is difficult, and often requires specific vaccination schema and the appropriate adjuvants to be effective. For gene-based vaccination against B16 melanoma in C57BL/6JNarl mice, initial priming with mouse RANTES cDNA followed 24 h later by human gp100 DNA vaccination, and later boosting with a viral vector expressing mRANTES and hgp100 strongly suppressed B16/hgp100 primary tumors and lung metastasis. The inclusion of mRANTES in this vaccination regimen gave significantly better suppression of tumor growth, substantially enhanced mouse survival, and led to greater cytotoxic activity of splenocytes against B16/hgp100 cells than vaccination against hgp100 alone. Our data demonstrate that co-vaccination with chemokine (mRANTES) and tumor specific (hgp100) genes in a specific time sequence is more effective at suppressing tumor growth and metastasis than hgp100 alone, and this effect may be mediated by sensitization of tumor cells to death ligands.

 

Co-researchers:Kandan Aravindaram, Hsiu-Hui Yu, Chun-Wen Lan, Pei-Hsueh Wang, Yun-Hsiang Chen, Hui-Ming Chen, Hideo Yagita