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Cellular & Molecular Immunology 2005年第5期2卷 331-341页

作者： Fan Yang~(1,2) Xiao-Feng Yang~(1,2,3) ~1Department of Pharmacology,Temple University School of Medicine,Philadelphia,Pennsylvania 19140,USA ~2Departments of Medicine and Immunology,Baylor College of Medicine,Houston,Texas 77030,USA Department of Pharmacology,Temple University School of Medicine,3420 N.Broad Street,Philadelphia,Pennsylvania 19140, Department of Pharmacology Temple University School of Medicine Philadelphia Pennsylvania 19140 USA.

The identification and molecular characterization of self-antigens expressed by human malignancies that are capable of elicitation of anti-tumor immune responses in patients have been an active field in tumor immunology. More than 2,000 tumor antigens have been identified, and most of these antigens are self-antigens. These significant progresses have led to the renaissance of tumor immunology and studies on anti-tumor immunotherapy. However, despite of the progress in the identification of self-tumor antigens, current antigen-specific immunotherapies for tumors are far less satisfied than expected, which reflects the urgent need to improve our understanding on self-tumor antigens. In order to develop more effective antigen specific anti-tumor immunotherapies and to monitor the responses to these immunotherapies in patients with tumors, many important fundamental questions need to be addressed. We propose for the first time that the studies in addressing the characteristics of self-tumor antigens and autoantigens are grouped as a new subject termed ＂antigenology＂. In this brief review, we would outline the progress in the identification of tumor antigens in solid tumors and hematologic malignancies, and overview the new concepts and principles of antigenology and their significance for future immunotherapies to these malignancies.

关键词： tumor tumor antigen new concept anti-tumor immune response immunotherapy

Establishment of a tumor-bearing Mouse Model Stably Expressing Human tumor antigens Survivin and MUC1 VNTRs

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Chemical Research in Chinese Universities 2012年第2期28卷 259-263页

作者： ZHANG Li-xing DU Jian-shi WANG Yu-qian LIU Chen-lu XIA Qiu ZHANG Xi-zhen CONG Xian-ling ZHANG Hai-hong China-Japan Union Hospital of Jilin University Changchun 130033P.R.China National Engineering Lab of AIDS Vaccine College of Life ScienceJilin UniversityChangchun 130012P.R.China

The eukaryotic vectors VR1012 expressing survivin or 33 tandem repeats of human mucin 1（MUC1）（VNTRs）,namely,VR1012-S and VR1012-VNTR（VNTR=variable number of tandem repeat）,were constructed by cloning survivin and VNTR genes into VR1012,*** eukaryotic vector pEGFP expressing survivin and MUC1 VNTRs fusion gene pEGFP-MS was also *** melanoma cell line（B16） stably expressing survivin and MUC1 VNTRs（MS ＋ B16） was established by Lipofectamine-mediated transfection of pEGFP-MS into B16 *** expression in MS ＋ B16 cells was observed using a fluorescent microscope and survivin and MUC1 VNTRs（MS） expression was confirmed by means of Western blot analysis.A syngenic graft tumor model was generated by subcutaneous injection of MS ＋ B16 cells into C57/BL6 mice and tumor size increased rapidly with time in a cell number dependent *** the third immunization,mice were challenged subcutaneously with 5×l0 5 MS ＋ B16 *** with that of the negative control immunized with phosphate-buffered saline（PBS）,a significant reduction of tumor growth was observed in groups immunized with survivin plasmid DNA and MUC1 VNTRs plasmid ***,the suppression of subcutaneous tumor was *** model is useful for the development of tumor vaccines targeting survivin and MUCI VNTRs.

关键词： Survivin MUC1 variable-number tandem repeat(MUC1 VNTR) tumor antigen tumor model tumor vaccine

Establishment of a tumor-bearing Mouse Model Stably Expressing EGFP Labeled Human MUC1 VNTRs

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Chemical Research in Chinese Universities 2008年第4期24卷 505-510页

作者： ZHANG Shu-zi ZHANG Hai-hong ZHANG Wa SHI He-liang YU Xiang-hui KONG Wei LI Wei Vaccine Research Center College of Life Science Jilin University Changchun 130012 P R. China

Two eukaryotic vectors expressing 9 tandem repeats of human MUCI（VNTR）, VR1012-VNTR, and pEGFP-VNTR, were constructed by cloning VNTR gene into VR1012 and pEGFP, respectively. VNTR stably expressing murine Lewis lung carcinoma（LLC） cell line（VNTR^＋ LLC） was established by Lipofectamine-mediated transfection of pEGFP-VNTR into LLC cells. The EGFP expression was observed under a fluorescent microscope and VNTR expression in VNTR^＋ LLC cells was confirmed by means of Western blotting. A syngenic graft tumor model was generated by subcutaneous injection of VNTR^＋ LLC cells into C57/BL6 mice and tumor size increased rapidly with time and in a cell qumber dependent manner. VNTR mRNA expression in the tumor formed was confirmed by RT-PCR. After the third immunization mice were challenged subcutaneously with 5×10^5 VNTR^＋ LLC cells, a significant reduction of subcutaneous tumor growth was observed in the groups immunized with VNTR plasmid DNA compared with that in the groups immunized with the vector DNA alone. Thus, the suppression of subcutaneous tumor was antigen-specific. This model is useful for the development of tumor vaccines targeting MUCI VNTRs.

关键词： MUCI VNTR tumor antigen tumor model tumor vaccine

Developing effective tumor vaccines: basis, challenges and perspectives

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Frontiers of Medicine 2007年第1期1卷 11-19页

作者： XU Qingwen CHEN Weifeng Department of Immunology Peking University Health Science CenterBeijing 100083China

A remarkable advance in tumor immunology during the last decade is the elucidation of the antigenic basis of tumor recognition and destruction.A variety of tumor antigens have been identified using several strategies including conventional experiments and newly developed *** these antigens,cancer/testis antigen(CT antigen)is considered to be the most promising target for immunotherapy by *** immunotherapy of tumors requires understanding of the natural relationship between the immune system and tumor in the status of differentiation,invasion and *** progress in development of effective cancer vaccines depends on the identification of appropriate target antigens,the establishment of optimal immunization strategies without harmful autoimmune responses and the ability of manipulating tumor microenvironment to circumvent immune suppression and to augment the anti-tumor immune response.

关键词： tumor vaccine tumor antigen CT antigen tumor microenvironment

Targeting tumor cells with antibodies enhances anti-tumor immunity

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Biophysics Reports 2018年第5期4卷 243-253页

作者： Zhichen Sun Yang-Xin Fu Hua Peng Key Laboratory of Infection and Immunity Institute of Biophysics Chinese Academy of Sciences University of Chinese Academy of Sciences Department of Pathology University of Texas Southwestern Medical Center

tumor-targeting antibodies were initially defined as a group of therapeutic monoclonal antibodies(mAb) that recognize tumor-specific membrane proteins, block cell signaling, and induce tumor-killing through Fc-driven innate immune responses. However, in the past decade, ample evidence has shown that tumor-targeting mAb(TTmAb) eradicates tumor cells via activation of cytotoxic T cells(CTLs). In this review, we specifically focus on how TTmAbs induce adaptive anti-tumor immunity and its potential in combination therapy with immune cytokines, checkpoint blockade, radiation, and enzymetargeted small molecule drugs. Exploring the mechanisms of these preclinical studies and retrospective clinical data will significantly benefit the development of highly efficient and specific TTmAb-oriented anti-tumor remedies.

关键词： Cytokine tumor microenvironment Innate immunity tumor antigen Targeting antibody Adaptive immunity

mRNA vaccine development for cholangiocarcinoma:a precise pipeline

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Military Medical Research 2023年第2期10卷 262-267页

作者： Tian-Yu Tang Xing Huang Gang Zhang Ming-Hao Lu Ting-Bo Liang Department of Hepatobiliary and Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Zhejiang Provincial Key Laboratory of Pancreatic Disease the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases Hangzhou 310003China Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province Hangzhou 310009China Cancer Center Zhejiang UniversityHangzhou 310058China

Cholangiocarcinoma(CHOL)is one of the most aggressive tumors worldwide and cannot be effectively treated by conventional and novel treatments,including immune checkpoint blockade *** mRNA vaccine-based immunotherapeutic strategy has attracted much attention for various diseases,however,its application in CHOL is limited due to the thoughtlessness in the integration of vaccine design and patient selection.A recent study established an integrated path for identifying potent CHOL antigens for mRNA vaccine development and a precise stratification for identifying CHOL patients who can benefit from the mRNA *** spite of a promising prospect,further investigations should identify immunogenic antigens and onco-immunological characteristics of CHOL to guide the clinical application of CHOL mRNA vaccines in the future.

关键词： Cholangiocarcinoma(CHOL) mRNA vaccine tumor antigen Immune subtype Immune microenvironment

Personalized pancreatic cancer therapy:from the perspective of mRNA vaccine

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Military Medical Research 2023年第4期10卷 461-477页

作者： Xing Huang Gang Zhang Tian‑Yu Tang Xiang Gao Ting‑Bo Liang Zhejiang Provincial Key Laboratory of Pancreatic Disease the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Department of Hepatobiliary and Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases Hangzhou 310003China The Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province Hangzhou 310009China Cancer Center Zhejiang UniversityHangzhou 310058China

Pancreatic cancer is characterized by inter-tumoral and intra-tumoral heterogeneity,especially in genetic alteration and *** therapeutic strategies for pancreatic cancer usually suffer resistance,highlighting the necessity for personalized precise *** vaccines have become promising alternatives for pancreatic cancer treatment because of their multifaceted advantages including multiple targeting,minimal nonspecific effects,broad therapeutic window,low toxicity,and induction of persistent immunological *** conventional vaccines based on the cells,microorganisms,exosomes,proteins,peptides,or DNA against pancreatic cancer have been developed;however,their overall efficacy remains *** with these vaccine modalities,messager RNA(mRNA)-based vaccines offer technical and conceptional advances in personalized precise treatment,and thus represent a potentially cutting-edge option in novel therapeutic approaches for pancreatic *** review summarizes the current progress on pancreatic cancer vaccines,highlights the superiority of mRNA vaccines over other conventional vaccines,and proposes the viable tactic for designing and applying personalized mRNA vaccines for the precise treatment of pancreatic cancer.

关键词： Pancreatic cancer Precise therapy Cancer vaccine mRNA vaccine tumor antigen Immune subtype

T-cell receptor-engineered T cells for cancer treatment： current status and future directions

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Protein & Cell 2018年第3期9卷 254-266页

作者： Yu Ping Chaojun Liu Yi Zhang Biotherapy Center The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 China Cancer Center The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 China Engineering Key Laboratory for Cell Therapy of Henan Province Zhengzhou 450052 China

T-cell receptor （TCR）-engineered T cells are a novel option for adoptive cell therapy used for the treatment of several advanced forms of cancer. Work using TCR- engineered T cells began more than two decades ago, with numerous preclinical studies showing that such cells could mediate tumor lysis and eradication. The success of these trials provided the foundation for clinical trials, including recent clinical successes using TCR- engineered T cells to target New York esophageal squamous cell carcinoma （NY-ESO-1）. These successes demonstrate the potential of this approach to treat cancer. In this review, we provide a perspective on the current and future applications of TCR-engineered T cells for the treatment of cancer. Our summary focuses on TCR activation and both pre-clinical and clinical applications of TCR-engineered T cells. We also discuss how to enhance the function of TCR-engineered T cells and prolong their longevity in the tumor microenvironment.

关键词： T-cell receptor tumor antigen TCR- engineered T cells neoantigen tumor microenvironment

Bacterial outer membrane vesicle-based cancer nanovaccines

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Cancer Biology & Medicine 2022年第9期19卷 1290-1300页

作者： Xiaoyu Gao Qingqing Feng Jing Wang Xiao Zhao CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety&CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of ChinaBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China Center of Drug Evaluation National Medical Products AdministrationBeijing 100022China IGDB-NCNST Joint Research Center Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China

tumor vaccines,a type of personalized tumor immunotherapy,have developed rapidly in recent *** vaccines evoke tumor antigen-specific T cells to achieve immune recognition and killing of tumor *** the immunogenicity of tumor antigens alone is insufficient,immune adjuvants and nanocarriers are often required to enhance anti-tumor immune *** present,vaccine carrier development often integrates nanocarriers and immune *** them,outer membrane vesicles(OMVs)are receiving increasing attention as a delivery platform for tumor *** are natural nanovesicles derived from Gramnegative bacteria,which have adjuvant function because they contain pathogen associated molecular ***,OMVs can be functionally modified by genetic engineering of bacteria,thus laying a foundation for applications as a delivery platform for tumor *** review summarizes 5 aspects of recent progress in,and future development of,OMV-based tumor nanovaccines:strain selection,heterogeneity,tumor antigen loading,immunogenicity and safety,and mass production of OMVs.

关键词： Cancer cancer vaccines outer membrane vesicles nanocarriers tumor antigen