MART-1 adenovirus-transduced dendritic cell immunization in a murine model of metastatic central nervous system tumor

J Neurooncol. Aug-Sep 2003;64(1-2):21-30. doi: 10.1007/BF02700017.

Abstract

Dendritic cells (DCs) are potent antigen-presenting cells that have been shown to play a critical role in the initiation of host immune responses against tumor antigens. In this study, a recombinant adenovirus vector encoding the melanoma-associated antigen, MART-1, was used to transduce murine DCs, which were then tested for their ability to activate cytotoxic T lymphocytes (CTLs) and induce protective immunity against B16 melanoma tumor cells implanted intracranially. Genetic modifications of murine bone marrow-derived DCs to express MART-1 was achieved through the use of an E1-deficient, recombinant adenovirus vector. Sixty-two C57BL/6 mice were immunized subcutaneously with AdVMART-1-transduced DCs (n = 23), untransduced DCs (n = 17), or sterile saline (n = 22). Using the B16 murine melanoma, which naturally expresses the MART-1 antigen, all the mice were then challenged intracranially with viable, unmodified syngeneic B16 tumor cells 7 days later. Splenocytes from representative animals in each group were harvested for standard cytotoxicity (CTL) and enzyme-linked immunospot (ELISPOT) assays. The remaining mice were followed for survival. Immunization of C57BL/6 mice with DCs transduced with an adenoviral vector encoding the MART-1 antigen elicited the development of antigen-specific CTL responses. As evidenced by a prolonged survival curve when compared to control-immunized mice with intracranial B16 tumors, AdMART-1-DC vaccination was able to elicit partial protection against central nervous system tumor challenge in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Antigens, Neoplasm
  • Brain Neoplasms / immunology*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / secondary*
  • Cytokines / biosynthesis
  • Dendritic Cells / immunology*
  • Female
  • Genetic Vectors
  • Immunization*
  • MART-1 Antigen
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / immunology*
  • Spleen / cytology
  • Spleen / metabolism
  • T-Lymphocytes, Cytotoxic / immunology
  • Transduction, Genetic*

Substances

  • Antigens, Neoplasm
  • Cytokines
  • MART-1 Antigen
  • Mlana protein, mouse
  • Neoplasm Proteins