Liposomal clodronate treatment for tumour macrophage depletion in dogs with soft‐tissue sarcoma

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  • A. M. Guth
    Animal Cancer Center, Department of Clinical Sciences Colorado State University Ft. Collins CO 80523 USA
  • S. D. Hafeman
    Animal Cancer Center, Department of Clinical Sciences Colorado State University Ft. Collins CO 80523 USA
  • R. E. Elmslie
    Veterinary Cancer Specialists Veterinary Referral Center of Colorado Englewood CO 80211 USA
  • S. W. Dow
    Animal Cancer Center, Department of Clinical Sciences Colorado State University Ft. Collins CO 80523 USA

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<jats:p>Increased numbers of tumour‐associated macrophages correlate with rapid tumour growth and metastasis in tumours. Thus, macrophage depletion has potential as a novel cancer therapy and positive responses have been reported in rodent tumour models. To investigate the effectiveness of this approach in dogs with cancer, we evaluated the effects of the macrophage‐depleting agent liposomal clodronate (<jats:styled-content style="fixed-case">LC</jats:styled-content>) in dogs with soft‐tissue sarcoma (<jats:styled-content style="fixed-case">STS</jats:styled-content>). To this end, we conducted a clinical trial of <jats:styled-content style="fixed-case">LC</jats:styled-content> therapy in 13 dogs with <jats:styled-content style="fixed-case">STS</jats:styled-content>. Repeated <jats:styled-content style="fixed-case">LC</jats:styled-content> administration was well tolerated clinically. Preliminary examination of tumour biopsy sets from 5 of the 13 dogs demonstrated that the density of <jats:styled-content style="fixed-case">CD11b<jats:sup>+</jats:sup></jats:styled-content> macrophages was significantly decreased after <jats:styled-content style="fixed-case">LC</jats:styled-content> treatment. Circulating concentrations of interleukin‐8 were also significantly reduced. These preliminary studies are the first to suggest that <jats:styled-content style="fixed-case">LC</jats:styled-content> can be used as a systemic macrophage‐depleting agent in dogs to reduce numbers of tumour‐associated macrophages.</jats:p>

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