Macrophage inflammatory protein 3α transgene attracts dendritic cells to established murine tumors and suppresses tumor growth Journal Article


Authors: Fushimi, T.; Kojima, A.; Moore, M. A. S.; Crystal, R. G.
Article Title: Macrophage inflammatory protein 3α transgene attracts dendritic cells to established murine tumors and suppresses tumor growth
Abstract: Dendritic cells (DCs) are powerful antigen-presenting cells that function as the principal activators of T cells. Since the human CC chemokine, macrophage inflammatory protein 3α (MIP-3α), is chemotactic for DCs in vitro, we hypothesized that adenovirus-mediated gene transfer of MIP- 3α (AdMIP-3α) to tumors might induce local accumulation of DCs and inhibit growth of preexisting tumors. AdMIP-3α directed expression of mRNA and protein in vitro, and the supernatant of A549 cells infected with AdMIP-3α was chemotactic for DCs. In vivo, injection of AdMIP-3α into subcutaneous tumors resulted in local expression of the MIP-3α cDNA and in the local accumulation of DCs. In four syngeneic tumor models, growth of established tumors was significantly inhibited compared with untreated tumors or tumors injected with control vector, and in all but the poorly immunogenic LLC carcinoma model, this treatment increased survival advantage of the preexisting tumors. In all four tumor models, intratumoral injection of AdMIP-3α induced the local accumulation of CD8b.2+ cells and elicited tumor-specific cytotoxic T-lymphocyte activity, and adoptive transfer of splenocytes of animals receiving this treatment protected against a subsequent challenge with the identical tumor cells. In wild-type but not in CD8-deficient mice, AdMIP-3α inhibited the growth of tumors. Finally, AdMIP- 3α also inhibited the growth of distant tumors. This strategy may be useful for enlisting the help of DCs to boost anti-tumor immunity against local and metastatic tumors without the necessity of ex vivo isolation and manipulation of DCs.
Keywords: controlled study; unclassified drug; nonhuman; lymphocytes, tumor-infiltrating; mouse; animals; mice; mice, knockout; animal tissue; cancer immunotherapy; dendritic cell; animal experiment; in vivo study; in vitro study; mice, inbred balb c; mice, inbred c57bl; genetic vectors; mice, transgenic; dendritic cells; cellular immunity; chemotaxis; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; gene therapy; neoplasms, experimental; adoptive transfer; tumor growth; antigen presenting cell; receptors, chemokine; adenoviridae; virus vector; immunity, cellular; adenovirus; chemokines, cc; macrophage inflammatory protein 3alpha; humans; female; priority journal; article; beta chemokine; macrophage inflammatory protein; macrophage inflammatory proteins
Journal Title: Journal of Clinical Investigation
Volume: 105
Issue: 10
ISSN: 0021-9738
Publisher: American Society for Clinical Investigation  
Date Published: 2000-05-15
Start Page: 1383
End Page: 1393
Language: English
PUBMED: 10811846
PROVIDER: scopus
PMCID: PMC315459
DOI: 10.1172/JCI7548
DOI/URL:
Notes: Export Date: 18 November 2015 -- Source: Scopus
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  1. Malcolm A S Moore
    549 Moore