Topical treatment of melanoma metastases with imiquimod, plus administration of a cancer vaccine, promotes immune signatures in the metastases

使用咪喹莫特局部治疗黑色素瘤转移,并注射癌症疫苗,可促进转移中的免疫特征

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作者:Ileana S Mauldin, Nolan A Wages, Anne M Stowman, Ena Wang, Walter C Olson, Donna H Deacon, Kelly T Smith, Nadedja Galeassi, Jessica E Teague, Mark E Smolkin, Kimberly A Chianese-Bullock, Rachael A Clark, Gina R Petroni, Francesco M Marincola, David W Mullins, Craig L Slingluff Jr

Conclusions

Four eligible patients were enrolled, and administration of imiquimod and vaccination were well tolerated. Circulating T cell responses to the vaccine was detected by ex vivo ELIspot assay in 3 of 4 patients. Treatment of metastases with imiquimod induced immune cell infiltration and favorable gene signatures in the patients with circulating T cell responses. This study supports further study of topical imiquimod combined with vaccines or other immune therapies for the treatment of melanoma.

Methods

Eligible patients were immunized with a vaccine comprised of 12 melanoma peptides and a tetanus toxoid-derived helper peptide, and imiquimod was applied topically to metastatic tumors daily. Adverse events were recorded, and effects on the tumor microenvironment were evaluated from sequential tumor biopsies. T cell responses were assessed by IFNγ ELIspot assay and T cell tetramer staining. Patient tumors were evaluated for immune cell infiltration, cytokine and chemokine production, and gene expression.

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