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Updated: Jun 21, 2026
A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Transgenic expression of human gp100 and RANTES at specific time points for suppression of melanoma
K Aravindaram1, H-H Yu, C-W Lan
1Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
Abstract:
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. The chemokine RANTES has been studied as a vaccine adjuvant in cancer therapy, but specific applications remain to be determined. 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. B16/hgp100 melanoma cells were resistant to the ligands TRAIL and FasL in vitro but sensitized to them in vivo owing to the priming effect of cytokines in response to vaccination. 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.
Insights
This study shows that combining chemokine (mRANTES) and tumor antigen (hgp100) gene vaccination effectively suppresses melanoma growth and metastasis. This novel approach enhances anti-tumor immunity and survival in mice.
Area of Science:
- Immunology
- Oncology
- Gene Therapy
Background:
- Inducing cell-mediated immunity against cancer is challenging.
- Chemokine RANTES shows potential as a vaccine adjuvant for cancer therapy.
Purpose of the Study:
- To evaluate the efficacy of a sequential gene-based vaccination strategy using mouse RANTES (mRANTES) and human gp100 (hgp100) for B16 melanoma treatment.
- To determine if mRANTES inclusion enhances anti-tumor responses compared to hgp100 vaccination alone.
Main Methods:
- Gene-based vaccination in C57BL/6JNarl mice using mRANTES cDNA priming, followed by hgp100 DNA vaccination, and viral vector boosting with mRANTES and hgp100.
- Assessment of tumor suppression, metastasis inhibition, mouse survival, and splenocyte cytotoxic activity against B16/hgp100 cells.
- In vitro and in vivo analysis of B16/hgp100 melanoma cell sensitivity to TRAIL and FasL.
Main Results:
- The combined mRANTES and hgp100 vaccination regimen significantly suppressed primary tumor growth and lung metastasis.
- Inclusion of mRANTES led to enhanced mouse survival and greater splenocyte cytotoxic activity compared to hgp100 alone.
- B16/hgp100 cells, resistant in vitro, became sensitized to death ligands in vivo due to vaccination-induced cytokines.
Conclusions:
- Sequential co-vaccination with mRANTES and hgp100 genes is a potent strategy for suppressing melanoma tumor growth and metastasis.
- The enhanced anti-tumor effect may be mediated by the sensitization of tumor cells to death ligands.
- This approach offers a promising avenue for cancer immunotherapy.
