mRNA-based dendritic cell immunization improves survival in ret transgenic mouse melanoma model

作者: Adi Sharbi-Yunger , Mareike Grees , Esther Tzehoval , Jochen Utikal , Viktor Umansky

DOI: 10.1080/2162402X.2016.1160183

关键词: CD44MelanomaBiologyImmune systemDendritic cellImmunotherapyGenetically modified mouseImmunologyCell activationCD8

摘要: Malignant melanoma is characterized by a rapid progression, metastasis to distant organs and resistance chemo radiotherapy. Although capable of eliciting an immune response, the disease progresses overall results immunotherapeutic clinical studies are not satisfactory. Recently, we have developed novel genetic platform for improving induction peptide-specific CD8(+) T cells dendritic cell (DC) based on membrane-anchored β2-microglobulin (β2m) linked selected antigenic peptide at N-terminus cytosolic domain TLR4 C-terminus. In vitro transcribed mRNA transfection antigen-presenting (APCs) resulted in efficient coupling presentation activation. this research, utilize chimeric induce response ret transgenic mice that spontaneously develop malignant skin examine its effect survival tumor-bearing mice. Following immunization with construct system, observe significantly prolonged as compared control group. Moreover, see elevations frequency CD62L(hi)CD44(hi) central CD62L(lo)CD44(hi) effector memory T-cell subsets. Importantly, do any changes frequencies regulatory (Tregs) myeloid-derived suppressor (MDSCs) vaccinated groups. Our data suggest vaccination approach could be efficiently applied immunotherapy melanoma.

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