Immunization against MUC18/MCAM, a novel antigen that drives melanoma invasion and metastasis.
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.
Leslie
M C
MC
Unit 173, Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Zhao
Y-J
YJ
Lachman
L B
LB
Hwu
P
P
Wu
G-J
GJ
Bar-Eli
M
M
D000524:Alphavirus / Q000235:genetics; D000818:Animals; D051929:CD146 Antigen / Q000235:genetics; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D007167:Immunotherapy / Q000379:methods; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness / Q000276:immunology; D009374:Neoplasms, Experimental; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage*
D051929:CD146 Antigen; C497902:MCAM protein, human; D019444:Vaccines, DNA