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 |
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Rok vydání: | 2000 |
Předmět: |
Cancer Research
medicine.medical_treatment Immunology Antigen presentation Melanoma Experimental Cross Reactions Biology Major histocompatibility complex Cancer Vaccines Epitope Interferon-gamma Mice MART-1 Antigen Antigen Antigens Neoplasm Vaccines DNA medicine Animals Humans Immunology and Allergy Cytotoxic T cell neoplasms Pharmacology integumentary system Histocompatibility Antigens Class I Vaccination Dendritic Cells Dendritic cell Immunotherapy Virology Neoplasm Proteins Mice Inbred C57BL Granzyme B Cancer research biology.protein Female Interleukin-4 Spleen T-Lymphocytes Cytotoxic |
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 |
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