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in situ vaccination and gene-medeiated PD-L1 blockade for enhanced tumor immunotherapy

Chinese Chemical Letters 2021年第5期32卷 1770-1774页

作者： Yingying Hu Lin Lin Zhaopei Guo Jie Chen Atsushi Maruyama Huayu Tian Xuesi Chen Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China University of Science and Technology of China Hefei 230026China Jilin Biomedical Polymers Engineering Laboratory Changchun 130022China Department of Life Science and Technology Tokyo Institute of TechnologyNagatsutaMidoriYokohama 226-8501Japan

Despite of the promising achievements of immune checkpoints blockade therapy(ICB) in the clinic,which was often limited by low objective responses and severe side ***,we explored a synergistic strategy to combine in situ vaccination and gene-mediated anti-PD therapy,which was generated by unmethylated cytosine-phosphate-guanine(CpG) and pshPD-L1 gene *** worked as the delivery carrier to co-deliver the CpG and pshPD-L1 genes,the formed PDC(PEI/DNA/CpG)nanoparticles were further shielded by aldehyde modified polyethylene glycol(OHC-PEG-CHO) via pH responsive Schiff base reaction for OHC-PEG-CHO-PEI/DNA/CpG nanoparticles(P(PDC) NPs) prepa *** steps could be finished within 30 *** simple nanoparticles achieved the synergistic antitumor efficacy in B16 F10 tumor-bearing mice,and the amplified T cell responses,together with enhanced NK cells infiltration were observed after the combined *** addition,the pH responsive delivery system reduced the side effects triggered by anti-PD *** facile and effective combination strategy we presented here might provide a novel treatment for tumor inhibition.

关键词： in situ vaccination CpG PD-L1 Immu notherapy Gene therapy

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Immune responses elicited by ssRNA(-) oncolytic viruses in the host and in the tumor microenvironment

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Journal of Cancer Metastasis and Treatment 2023年第1期9卷 285-306页

作者： Yonina Bykov Gloria Dawodu Aryana Javaheri Adolfo Garcia-Sastre Sara Cuadrado-Castano Department of Microbiology Icahn School of Medicine at Mount SinaiNew YorkNY 10029USA Department of Medicine Icahn School of Medicine at Mount SinaiNew YorkNY 10029USA Global Health and Emerging Pathogens Institute Icahn School of Medicine at Mount SinaiNew YorkNY 10029USA The Tisch Cancer Institute Icahn School of Medicine at Mount SinaiNew YorkNY 10029USA Department of Pathology Molecular and Cell-Based MedicineIcahn School of Medicine at Mount SinaiNew YorkNY 10029USA

Oncolytic viruses(OVs)are at the forefront of biologicals for cancer *** represent a diverse landscape of naturally occurring viral strains and genetically modified viruses that,either as single agents or as part of combination therapies,are being evaluated in preclinical and clinical *** the field gains momentum,the research on OVs has been shifting efforts to expand our understanding of the complex interplay between the virus,the tumor and the immune system,with the aim of rationally designing more efficient therapeutic ***,the potential of an OV platform is no longer defined exclusively by the targeted replication and cancer cell killing capacities of the virus,but by its contribution as an immunostimulator,triggering the transformation of the immunosuppressive tumor microenvironment(TME)into a place where innate and adaptive immunity players can efficiently engage and lead the development of tumor-specific long-term memory *** we review the immune mechanisms and host responses induced by ssRNA(-)(negative-sense single-stranded RNA)viruses as OV *** focus on two ssRNA(-)OV candidates:Newcastle disease virus(NDV),an avian paramyxovirus with one of the longest histories of utilization as an OV,and influenza A(IAV)virus,a well-characterized human pathogen with extraordinary immunostimulatory capacities that is steadily advancing as an OV candidate through the development of recombinant IAV attenuated platforms.

关键词： Oncolytic virus NDV IAV virotherapy paramyxovirus orthomyxovirus ssRNA(-) immunotherapy cancer vaccine ICD in situ vaccination tumor microenvironment

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