Current Cancer Drug Targets

Ruiwen Zhang 
Texas Tech University Health Sciences Center
1300 Coulter Drive
Amarillo, TX 79106
USA

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Intramammary Application of Non-Methylated-CpG Oligodeoxynucleotides (CpG) Inhibits both Local and Systemic Mammary Carcinogenesis in Female BALB/c Her-2/neu Transgenic Mice

Author(s): Cristina Mastini, Pablo D. Becker, Manuela Iezzi, Claudia Curcio, Piero Musiani, Guido Forni, Federica Cavallo, Carlos A. Guzman.

Abstract:

CpG are powerful drugs activating the innate immune system. In this study, the ability of their intramammary administration in impeding the devastating progression of carcinogenesis in all the mammary glands of female BALB/c mice transgenic for the rat neu transforming oncogene was assessed. Starting when in situ carcinomas were scattered over all their mammary glands (week 10), mice received CpG injections in the stroma of the fourth left gland. Local neoplastic progression was inhibited by six monthly administrations. CpG not only delayed the onset of carcinomas in the injected gland, but also hampered their progression. Extended latency was observed for tumors in glands both close to and far from the injection site. When the experiment ended (week 45), no tumors were palpable in 67% of the injected glands and a markedly impaired tumor growth was evident in the others. An impressive local infiltrate of CD11b+ cells with the morphologic features of macrophages, plasma cells, B220+ B cells, and CD4+ and CD8+ T cells was quickly recruited to the CpG-treated glands. High quantities of IFN-γ producing cells were only present in the ipsilateral axillary draining lymph nodes of the treated glands. Enhanced natural killer (NK) lytic activity was also detected in the spleens. Inhibition of progression was weaker when only four injections were given, and abolished by in vivo depletion of NK cells. CpG monotherapy is thus effective in an aggressive model of autochthonous cancer. The results strongly support the administration of CpG as a local monotherapy of multiple invasive microscopic lesions.

Keywords: Her-2/neu, CpG, NK cells

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Article Details

VOLUME: 8
ISSUE: 3
Year: 2008
Page: [230 - 242]
Pages: 13
DOI: 10.2174/156800908784293604
Price: $58