Human Flt3L generates dendritic cells from canine peripheral blood precursors: implications for a dog glioma clinical trial

人类 Flt3L 从犬外周血前体细胞产生树突状细胞:对犬神经胶质瘤临床试验的意义

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作者:Weidong Xiong, Marianela Candolfi, Chunyan Liu, A K M Ghulam Muhammad, Kader Yagiz, Mariana Puntel, Peter F Moore, Julie Avalos, John D Young, Dorothy Khan, Randy Donelson, G Elizabeth Pluhar, John R Ohlfest, Kolja Wawrowsky, Pedro R Lowenstein, Maria G Castro

Background

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults and carries a dismal prognosis. We have developed a conditional cytotoxic/immunotherapeutic approach using adenoviral vectors (Ads) encoding the immunostimulatory cytokine, human soluble fms-like tyrosine kinase 3 ligand (hsFlt3L) and the conditional cytotoxic molecule, i.e., Herpes Simplex Type 1- thymide kinase (TK). This therapy triggers an anti-tumor immune response that leads to tumor regression and anti-tumor immunological memory in intracranial rodent cancer models. We

Significance

These results demonstrate that hsFlt3L induces the proliferation of canine DCs and support its use in upcoming clinical trials for canine GBM. Our data further support the translation of hsFlt3L to be used for dendritic cells' vaccination and gene therapeutic approaches from rodent models to canine patients and its future implementation in human clinical trials.

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