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

  • Tumor Immunology: Steps And Principles
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Summary

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 challengein vivo.

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Authors and Affiliations

  1. Division of Neurosurgery and the Jonsson Comprehensive Cancer Center, University of California at Los Angeles School of Medicine, Los Angeles, CA, USA

    Howard Broder, Andrea Anderson, Thomas J. Kremen, Sylvia K. Odesa & Linda M. Liau

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  1. Howard Broder
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  2. Andrea Anderson
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  3. Thomas J. Kremen
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  4. Sylvia K. Odesa
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  5. Linda M. Liau
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Correspondence to Linda M. Liau.

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Broder, H., Anderson, A., Kremen, T.J. et al. MART-1 adenovirus-transduced dendritic cell immunization in a murine model of metastatic central nervous system tumor. J Neuro-Oncol 64, 21–30 (2003). https://doi.org/10.1007/BF02700017

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