Generation of T-Cell Immunity to a Murine Melanoma Using MART-1–Engineered Dendritic Cells

Autor: Saral N. Amarnani, Antoni Ribas, John A. Glaspy, Andrew Koh, Billy Hu, Vivian B. Dissette, William H. McBride, Angela Y. Chen, Lisa H. Butterfield, James S. Economou
Rok vydání: 2000
Předmět:
Zdroj: Journal of Immunotherapy. 23:59-66
ISSN: 1524-9557
DOI: 10.1097/00002371-200001000-00008
Popis: Summary: The murine melanoma B16 expresses the murine counterpart of the human MART-1/Melan-A (MART-1) antigen, sharing a 68.6% amino acid sequence identity. In this study, mice were vaccinated with bone marrow–derived murine dendritic cells genetically modified with a replication-incompetent adenoviral vector to express the human MART-1 gene (AdVMART1). This treatment generated a protective response to a lethal tumor challenge of unmodified murine B16 melanoma cells. The response was mediated by major histocompatibility complex class I–restricted cytotoxic T lymphocytes specific for MART-1 antigen, which produced high levels of interferon-γ when reexposed to MART-1 in vitro and lysed targets in a calcium-dependent mechanism suggestive of perforin/granzyme B lysis. MART-1 was presented by the dendritic cells used for vaccination and not by epitopes cross-presented by host antigen-presenting cells. In conclusion, dendritic cells genetically modified to express the human MART-1 antigen generate potent murine MART-1–specific protective responses to B16 melanoma.
Databáze: OpenAIRE