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第十一届全国化学生物学学术会议

作者：王均 Song Shen Cheng-Tao Jiang Kai-Ge Chen An Liu 华南理工大学 School of Biomedical Sciences and Engineering Guangzhou International CampusSouth China University of Technology

Antibodies are important therapeutic agents for cancer,and antibodies blocking the negative regulators of T cells function（known as immune checkpoints） represent the predominant modality of cancer *** remarkable progress,current immunotherapeutic antibodies-based treatments still have many *** immunotherapy has recently emerged as a powerful cancer treatment strategy,and extensive clinical efforts are currently underway to examine efficacy of combining checkpoint inhibitors with each other,but improved efficacy comes at the cost of disabling side *** an alternative combination approach,bispecific antibodies（BsAbs）,which contain two different antigen-binding sites in one molecule,are now emerging as a growing class of immunotherapies[1,2].Inspired by the unique characteristic of BsAbs,we attempt to construct a nano-platform to convenient and efficient bind two or more categories of immunotherapeutic antibodies in clinical or preclinical development,and form multivalent *** choosing proper antagonistic and/or agonistic antibodies,multivalent nanoantibodies could activate immune effector cells（e.g.,T cells,NK cells and macrophages） and enhance interaction between effector cells and tumour cells via binding corresponding targets on both cells,resulting superior antitumor effect.

关键词： cancer immunotherapy bispecific antibodies multivalent Nano-antibodies

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Large-cohort humanized NPI mice reconstituted with CD34+ hematopoietic stem cells are feasible for evaluating preclinical cancer immunotherapy

Large-cohort humanized NPI mice reconstituted with CD34+ hem...

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第十四届全国免疫学学术大会

作者： Xiongfei Xu Haihui Gu Hongwei Li Suizhi Gao Xiaohan Shi Jing Shen Bo Li Huan Wang Kailian Zheng Zhuo Shao Siying Peng Yongzhan Nie Zhaoshen Li Shiwei Guo Baohua Qian Gang Jin Changhai Hospital Second Military Medical University 空军军医大学附属西京医院

cancer immunotherapy has achieved impressive therapeutic effects in many cancers, while only a small subset of patients benefit from it and even some patients have experienced severe toxicity. It is urgent to develop a feasible large-cohort humanized mouse model to evaluate pre-clinical efficacy and safety in cancer immunotherapy. Furthermore, developing potentially effective combination therapy between cancer immunotherapy and other therapies also needs humanized mouse model to adequately mimic clinical actual setting. Herein, we established a humanized mouse model engrafted with less human CD34

关键词： humanized mouse T cell cancer immunotherapy checkpoint blockade chimeric antigen receptor T cell Bispecific antibody

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NSR on PMN-MDSCs is a potential target for cancer immunotherapy

NSR on PMN-MDSCs is a potential target for cancer immunother...

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第十四届全国免疫学学术大会

作者： Min Luo Zhigang Lu Fudan University

Polymorphonuclear myeloid-derived suppressor cells(PMN-MDSCs) are pathologically activated neutrophils that are crucial for immune regulation in cancer. Currently, specific therapeutic target of PMN-MDSC is still lacking. Here, by RNAseq analysis and an in vivo CRISPR-Cas9 screening of PMN-MDSC-related membrane proteins, we identified a neutrophil specific receptor-NSR, which was upregulated in PMN-MDSCs compared to normal neutrophils. Knockout of NSR in mice does not alter the development of immune system, however, it significantly inhibits tumor growth in multiple tumor xenograft models. Single cell RNA sequencing revealed that NSR knockout reversed tumor immune-suppressive microenvironment, with substantial reduction of PMN-MDSCs and elevated CD8 T cell infiltration. NSR plays critical roles in the migration and T cell suppression of PMN-MDSCs through the downstream S100A8/A9. Competitive blockade of NSR by NSR extracellular domain(ECD) administration phenocopies NSR knockout in tumor suppression and mice survival, and showed a significant synergy effect with PD1 antibody. Aberrant expression of human NSR(hNSR) was detected in multiple cancer types, and unfavorably correlated with the overall survival of melanoma patients. With NSR humanized mice, we demonstrated that hNSR is functional homolog of mNSR, and blockage of hNSR also significantly inhibited the growth of B16 tumor. Our study identified NSR as a critical receptor on PMN-MDSCs for the establishment of tumor immune suppressive microenvironment, providing a novel and safe target for cancer immunotherapy.

关键词： Polymorphonuclear myeloid-derived suppressor cells(PMN-MDSCs) NR-1 cancer immunotherapy

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A Novel IDO Inhibitor Candidate for cancer immunotherapy

A Novel IDO Inhibitor Candidate for Cancer immunotherapy

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第十二届全国免疫学学术大会

作者：许光伟黄志王天琪范艳史毅向荣南开大学

Indoleamine 2,3-dioxygenase(IDO) is a monomeric heme-containing oxidoreductase that catalyzes tryptophan degradation in the first,rate-limiting step along the kynurenine *** is emerging as a novel immunotherapeutic target for cancer treatment recently due to its immunosuppressive roles for tumor cells to escape the immune ***,we discovered a novel IDO inhibitor by screening the SPECS Chemical molecular library,namely TD27,which exhibits strong inhibitory activity on IDO at nanomolar *** function in the modulation of immune cells and therefore its therapeutic potential as an anticancer agent were also tested in vitro and in ***27 dramatically promoted the proliferation of T cells and reduced the number of regulatory T cell(Tregs).In melanoma(B16F10) tumor-bearing mice,TD27 significantly inhibited IDO activity and suppressed tumor *** addition,TD27 can reduce the numbers of Foxp3 Tregs,which are known to prevent the development of efficient antitumor immune *** results suggested that TD27 might be an attractive cancer therapeutic candidate.

关键词： IDO Melanoma cancer immunotherapy

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Functional nanomaterials for immune regulation and cancer immunotherapy

Functional nanomaterials for immune regulation and cancer im...

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第十二届全国免疫学学术大会

作者： Wang Yi Wang Hao National Center for Nanoscience and Technology

immunotherapy has become a promising treatment for a variety of cancers and increasing evidences indicated that regulating immune systems make crucial contribution to the antitumor *** were several well-established ca... 详细信息

关键词： nanomaterials autophagy cancer immunotherapy macrophages dendritic cells

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Novel STING agonists mediate effective tumor regression that synergizes with checkpoint inhibitors for cancer immunotherapy

Novel STING agonists mediate effective tumor regression that...

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第十三届全国免疫学学术大会

作者： Fabienne Vernejoul Cedric Boularan Thierry Lioux Anne-Sophie Baudru Marc-Antoine Maunv Alain Lamoureux Gerard Tiraby Eric Perouzel Michele Tiraby InvivoGen

The lack of response of a majority of cancer patients to immune checkpoint blockade is attributed to insufficient T cell priming and infiltration into the tumor microenvironment. The administration of cyclic dinucleotides(CDNs) represents a clinical opportunity to overcome this limitation. By activating effector cells, these agonists of the STING innate immune pathway are known to generate significant T-cell priming and thereby to mediate potent tumor regression. In this study, we evaluated the efficacy of intratumoralinjection of two new synthetic STING agonists in multiple aggressive mouse tumor models including B16 melanoma and CT26 colon carcinoma. The first one CL592 is a natural phosphodiester-based CDN with a structure inspired from 3’3’-cGAMP and the second one CL656 is a fluoroCDN with phosphorothioatelinkage optimized for potency. The properties of both molecules will be discussed in view of their use in combination with immune checkpoint inhibitors(ICI) for cancer immunotherapy.

关键词： STING Checkpoint cancer immunotherapy

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Peptide inhibitors blocking PD-1/PD-L1 interaction for cancer immunotherapy

Peptide inhibitors blocking PD-1/PD-L1 interaction for cance...

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第十届全国免疫学学术大会

作者： Beiyuan Liu Haonan Chang Yuanming Qi Lei Liu Yanfeng Gao School of Life Sciences Zhengzhou University Department of Chemistry Tsinghua University

Aim:Blockade of the protein-protein interaction between the transmembrane programmed cell death 1 protein(PD-1)and its ligand PD-L1 emerges as a promising immunotherapy for treating ***:The protein of PD-L1-Ig V was expressed in ***,and the isomer D-PD-L1-Ig V was synthesized by chemical *** peptides were screened by phage displayed *** affinity was tested by BIAcore and ***

关键词： cancer immunotherapy Therapeutic peptide Mirror-image phage display Protein chemical synthesis PD-1

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Inorganic Nanoparticles for Delivery and cancer immunotherapy

Inorganic Nanoparticles for Delivery and Cancer Immunotherap...

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中国化学会第十届全国无机化学学术会议

作者： Chengzhong Yu Australian Institute for Bioengineering and Nanotechnology The University of Queensland School of Chemistry and Molecular Engineering East China Normal University

Engineered inorganic nanoparticles, such as silica, iron oxide, aluminum oxide and their composites have been applied for various drug delivery applications, conventionally as carriers. When nanoparticles are selected as drug delivery systems, one may ask three questions: why nanoparticles, where to deliver and what to deliver? For the first question, we have demonstrated the advantages of silica-based nanoparticles from four aspects. 1. Nanoparticle surface roughness and delivery performance. We have shown that silica nanoparticles with a rough surface are better delivery vehicles for pDNA, siRNA and proteins. 2. Nanoparticle composition and adjuvanticity. We have shown that the composition of nanoparticles is important as both adjuvants and delivery vehicles in promoting immune responses. 3. Nanoporous structure and bioavailability. It is shown that the pore sizes of ordered mesoporous silica materials can be adjusted at sub-nm precision. A pore size – solubility relationship is obtained which provides a novel strategy to improve the bioavailability of hydrophobic drugs. 4. Nanoparticle asymmetry and adjuvanticity. We have prepared mesoporous silica nanoparticles with asymmetrical structures. The asymmetrical nanoparticles exhibited a higher level of uptake and maturation of antigen presenting cells compared to conventional symmetrical ones;and delivered an antigen peptide in vivo with improved immune response. We will answer the second and third questions relevant to applications of nanoparticles, with highlights given to applications for sustainable ecology and healthcare. Understanding the relationship between structure and property of inorganic nanoparticles holds promise in the design of advanced inorganic nanoparticles with unprecedented functionalities, not limited as carriers. We will demonstrate how to use classic iron oxide and alumina-silica chemistry in activating immune systems for vaccine delivery and cancer immunotherapy.

关键词： inorganic nanoparticles drug delivery cancer immunotherapy nano-pesticide vaccine

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Paradox-driven adventures in the development of cancer immunology and immunotherapy

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Genes & Diseases 2019年第3期6卷 224-231页

作者： Whitney Barham Joanina K.Gicobi Yiyi Yan Roxana S.Dronca Haidong Dong Mayo Clinic Medical Scientist Training Program Mayo ClinicRochesterMNUSA Mayo Clinic Graduate School of Biomedical Sciences Mayo ClinicRochesterMNUSA Department of Immunology Mayo ClinicRochesterMNUSA Department of Urology Mayo ClinicRochesterMNUSA Department of Medical Oncology Mayo ClinicRochesterMNUSA Division of Hematology and Medical Oncology Mayo ClinicJacksonvilleFLUSA

After more than one hundred years of documented trials,immunotherapy has become a standard of care in the treatment of human *** of the knowledge that led to recent breakthroughs seems quite logical from today’s point of ***,what we now cite as facts were originally considered paradoxes,meaning something contrary to expectations or perceived opinion at the *** order to make gains in the field of immunotherapy,one had to be willing to confront ideas and concepts that seemed to contradict one another,and reconcile how each could be *** is what led to new knowledge and ***,we highlight some of these paradoxes and the milestone discoveries that followed,each one critical for our understanding of immune checkpoint *** outlining some of the steps that we took and the challenges that we overcame,we hope to inspire and encourage future generations of researchers to confront the paradoxes that still permeate the field.

关键词： Biomarker cancer immunotherapy Cytotoxic T cells Hyperprogression Immune checkpoints PD-L1 PD-1

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Engineering nanomedicines for immunogenic eradication of cancer cells:Recent trends and synergistic approaches

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2475-2504页

作者： Ahmed O.Elzoghby Omar Samir Hagar E.Emam Ahmed Soliman Riham M.Abdelgalil Yomna M.Elmorshedy Kadria A.Elkhodairy Mahmoud L.Nasr Division of Engineering in Medicine and Division of Renal Medicine Department of MedicineBrigham and Women's HospitalHarvard Medical SchoolBoston 02115MAUSA cancer Nanotechnology Research Laboratory(CNRL) Faculty of PharmacyAlexandria UniversityAlexandria 21521Egypt

Resistance to cancer immunotherapy is mainly attributed to poor tumor immunogenicity as well as the immunosuppressive tumor microenvironment(TME)leading to failure of immune *** therapeutic strategies including chemotherapy,radiotherapy,photodynamic,photothermal,magnetic,chemodynamic,sonodynamic and oncolytic therapy,have been developed to induce immunogenic cell death(ICD)of cancer cells and thereby elicit immunogenicity and boost the antitumor immune ***,many challenges hamper the clinical application of ICD inducers resulting in modest immunogenic ***,we outline the current state of using nanomedicines for boosting ICD of cancer ***,synergistic approaches used in combination with ICD inducing nanomedicines for remodeling the TME via targeting immune checkpoints,phagocytosis,macrophage polarization,tumor hypoxia,autophagy and stromal modulation to enhance immunogenicity of dying cancer cells were *** further highlight the emerging trends of using nanomaterials for triggering amplified ICD-mediated antitumor immune *** reticulum localized ICD,focused ultrasound hyperthermia,cell membrane camouflaged nanomedicines,amplified reactive oxygen species(ROS)generation,metallo-immunotherapy,ion modulators and engineered bacteria are among the most innovative *** challenges,merits and demerits of ICD inducer nanomedicines were also discussed with shedding light on the future role of this technology in improving the outcomes of cancer immunotherapy.

关键词： Immunogenic cell death Immunogenic eradication Nanomedicines Drug delivery cancer immunotherapy Antitumor immunity T cells Tumor associated antigens Synergistic immune response

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