Original Article
Gene Therapy (2007) 14, 316–323. doi:10.1038/sj.gt.3302864; published online 5 October 2006
Immunization against MUC18/MCAM, a novel antigen that drives melanoma invasion and metastasis
M C Leslie1, Y-J Zhao1, L B Lachman2, P Hwu3 and M Bar-Eli1
- 1Unit 173, Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
- 2Unit 173, Department of Experimental Therapeutic, University of Texas MD Anderson Cancer Center, Houston, TX, USA
- 3Unit 173, Department of Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA
Correspondence: Dr M Bar-Eli, Unit 173, Department of Cancer Biology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. E-mail: mbareli@mdanderson.org
Received 19 June 2006; Revised 28 July 2006; Accepted 8 August 2006; Published online 5 October 2006.
Abstract
Melanoma patients with metastases have a very low survival rate and limited treatment options. Therefore, the targeting of melanoma cells when they begin to invade and metastasize would be beneficial. An adhesion molecule that is upregulated at the vertical growth phase is the melanoma cell adhesion molecule (MCAM/MUC18). MUC18 is expressed in late primary and metastatic melanoma with little or no expression on normal melanocytes. We utilized the alphavirus-based DNA plasmid, SINCp, encoding murine MUC18 (SINCp c-muMUC18) for vaccination against B16F10 murine melanoma cells expressing murine MUC18. This vaccine effectively protected mice from lethal challenges with melanoma-expressing murine MUC18 in both primary and metastatic tumor models. Vaccination against MUC18 elicited effective humoral and CD8+ T-cell immune responses against melanoma. We propose that targeting molecules important in tumor invasion may be useful in the design of future strategies for the prevention and treatment of melanoma.
Keywords:
MUC18/MCAM, melanoma, vaccine
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