Synthetic immunology and future NK cell immunotherapy

BI Jiacheng; TIAN Zhigang

doi:10.12211/2096-8280.2021-075

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Synthetic immunology and future NK cell immunotherapy

Invited Review | 更新时间：2025-03-20

- Synthetic immunology and future NK cell immunotherapy
- Synthetic Biology Journal Vol. 3, Issue 1, Pages: 22-34(2022)
- 作者机构：
  
  1.中国科学院深圳先进技术研究院，深圳合成生物学创新研究院，广东深圳 518055
  2.中国科学技术大学免疫学研究所，安徽合肥 230027
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2021-075
  CLC： R 392.12
- Received：19 July 2021，
  
  Revised：2021-10-20，
  
  Published：28 February 2022
- 稿件说明：
移动端阅览
毕嘉成，田志刚. 合成免疫学与未来NK细胞免疫治疗［J］. 合成生物学， 2022， 3（1）： 22-34

BI Jiacheng， TIAN Zhigang. Synthetic immunology and future NK cell immunotherapy［J］. Synthetic Biology Journal， 2022， 3（1）： 22-34
毕嘉成，田志刚. 合成免疫学与未来NK细胞免疫治疗［J］. 合成生物学， 2022， 3（1）： 22-34 DOI： 10.12211/2096-8280.2021-075.

BI Jiacheng， TIAN Zhigang. Synthetic immunology and future NK cell immunotherapy［J］. Synthetic Biology Journal， 2022， 3（1）： 22-34 DOI： 10.12211/2096-8280.2021-075.

摘要

近年来，免疫治疗在肿瘤等重大疾病治疗领域取得了突破性的进展，然而当前免疫治疗在应对实体瘤等方面的有效性和安全性仍有待提高。另一方面，合成生物学的理念和技术也取得了长足的发展，其与免疫学基础研究及免疫治疗实践相融合，诞生了“合成免疫学”新学科，后者将驱动免疫治疗的进一步发展。本文概述了肿瘤免疫治疗的现状及合成免疫学诞生的背景，对天然杀伤细胞（NK细胞）在肿瘤免疫中的作用及NK细胞疗法进行了介绍，并详细综述了设计构建合成免疫细胞和合成免疫分子的相关进展。研究表明，NK细胞由于其独特的属性，可能是“通用型”合成免疫细胞疗法的理想底盘细胞，通过精准识别肿瘤的嵌合抗原受体及智能响应性基因回路等的装载，将实现NK细胞的功能增效，并在NK细胞大规模扩增技术及封闭式、自动化、可编程“细胞工厂”等的支撑下，实现合成免疫细胞的“货架式”供应模式。除了合成免疫细胞疗法之外，减毒增效的合成免疫分子则为人工操控免疫应答提供了更多的可能性。展望未来，合成免疫学驱动的免疫细胞疗法将与新型的合成免疫分子相辅相成，进一步提高抗肿瘤免疫疗法的有效性和安全性。

Abstract

In recent years

immunotherapy has been a breakthrough for clinical treatment of major diseases

such as cancers

whose efficacy and safety in treatment of solid tumors

however

requires further improvements. Meanwhile

the concept and technologies of synthetic biology have also gained substantial development

along with studies on basic immunology and practices in the immunotherapy

giving birth to a new discipline

'synthetic immunology'. Synthetic immunology aims to engineer biological devices or equipments to reshape

renormalize and rebuild the immune system for rational manipulation of immune responses in immunotherapy against major diseases. This review focuses on the development of immunotherapy driven by synthetic immunology. For future synthetic immune cell therapy

the chassis cell is the key element. Among effector immune cells

Natural Killer (NK) cells are cytotoxic innate lymphocytes that recognize and kill tumor cells without the need for priming. NK-based cell therapy

with proven tolerability and efficacy against tumors

is known for its low toxicity and suitable for allogenic use. These unique features of NK cells make them a potentially ideal chassis for future 'universal' synthetic immune cell therapy

whose anti-tumor efficacy could be further strengthened by arming of NK-adapted chimeric antigen receptors for precise recognition of tumors and of gene circuits for intelligent responses against tumors. In addition

technologies such as large-scale expansion and closed

automatic

and programmable 'cell factory' will lay the essential basis for 'off-the-shelf' supply of these synthetic immune cells. Besides synthetic immune cell therapy

synthetic immune molecules represent another arm of future synthetic immunology-driven immunotherapy. High-throughput technologies

multi-omics

and humanized mouse models will aid the rational design of these synthetic molecules towards reduced toxicity and enhanced efficacy

thus providing more possibilities for manipulation of immune responses. In the future

synthetic immune molecules will cooperate with synthetic immune cell therapy to further improve the efficacy and safety of anti-tumor immune therapy.

关键词

Keywords

references

ZHANG Y Y , ZHANG Z M . The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications [J ] . Cellular & Molecular Immunology , 2020 , 17 ( 8 ): 807 - 821 .

KRUGER S , ILMER M , KOBOLD S , et al . Advances in cancer immunotherapy 2019-latest trends [J ] . Journal of Experimental & Clinical Cancer Research , 2019 , 38 ( 1 ): 268 .

VOENA C , CHIARLE R . Advances in cancer immunology and cancer immunotherapy [J ] . Discovery Medicine , 2016 , 21 ( 114 ): 125 - 133 .

SHARMA P , ALLISON J P . Dissecting the mechanisms of immune checkpoint therapy [J ] . Nature Reviews Immunology , 2020 , 20 ( 2 ): 75 - 76 .

SHARMA P , ALLISON J P . The future of immune checkpoint therapy [J ] . Science , 2015 , 348 ( 6230 ): 56 - 61 .

WEBER E W , MAUS M V , MACKALL C L . The emerging landscape of immune cell therapies [J ] . Cell , 2020 , 181 ( 1 ): 46 - 62 .

PETTITT D , ARSHAD Z , SMITH J , et al . CAR-T cells: A systematic review and mixed methods analysis of the clinical trial landscape [J ] . Molecular Therapy , 2018 , 26 ( 2 ): 342 - 353 .

JUNE C H , O'CONNOR R S , KAWALEKAR O U , et al . CAR T cell immunotherapy for human cancer [J ] . Science , 2018 , 359 ( 6382 ): 1361 - 1365 .

ZHANG C , HU Y , XIAO W H , et al . Chimeric antigen receptor-and natural killer cell receptor-engineered innate killer cells in cancer immunotherapy [J ] . Cellular & Molecular Immunology , 2021 , 18 ( 9 ): 2083 - 2100 .

KLICHINSKY M , RUELLA M , SHESTOVA O , et al . Human chimeric antigen receptor macrophages for cancer immunotherapy [J ] . Nature Biotechnology , 2020 , 38 ( 8 ): 947 - 953 .

ROSENBERG S A , RESTIFO N P . Adoptive cell transfer as personalized immunotherapy for human cancer [J ] . Science , 2015 , 348 ( 6230 ): 62 - 68 .

HEGDE P S , CHEN D S . Top 10 challenges in cancer immunotherapy [J ] . Immunity , 2020 , 52 ( 1 ): 17 - 35 .

PEI L , SCHMIDT M , WEI W . Synthetic biology: an emerging research field in China [J ] . Biotechnology Advances , 2011 , 29 ( 6 ): 804 - 814 .

KATZ L , CHEN Y Y , GONZALEZ R , et al . Synthetic biology advances and applications in the biotechnology industry: a perspective [J ] . Journal of Industrial Microbiology and Biotechnology , 2018 , 45 ( 7 ): 449 - 461 .

BREITLING R , TAKANO E . Synthetic biology advances for pharmaceutical production [J ] . Current Opinion in Biotechnology , 2015 , 35 : 46 - 51 .

MCDANIEL R , WEISS R . Advances in synthetic biology: on the path from prototypes to applications [J ] . Current Opinion in Biotechnology , 2005 , 16 ( 4 ): 476 - 483 .

ROYBAL K T , LIM W A . Synthetic immunology: hacking immune cells to expand their therapeutic capabilities [J ] . Annual Review of Immunology , 2017 , 35 : 229 - 253 .

GEERING B , FUSSENEGGER M . Synthetic immunology: modulating the human immune system [J ] . Trends in Biotechnology , 2015 , 33 ( 2 ): 65 - 79 .

VIVIER E , TOMASELLO E , BARATIN M , et al . Functions of natural killer cells [J ] . Nature Immunology , 2008 , 9 ( 5 ): 503 - 510 .

ABEL A M , YANG C , THAKAR M S , et al . Natural killer cells: Development, maturation, and clinical utilization [J ] . Frontiers in Immunology , 2018 , 9 : 1869 .

GEIGER T L , SUN J C . Development and maturation of natural killer cells [J ] . Current Opinion in Immunology , 2016 , 39 : 82 - 89 .

BI J C , TIAN Z G . NK cell exhaustion [J ] . Frontiers in Immunology , 2017 , 8 : 760 .

RAULET D H . Missing self recognition and self tolerance of natural killer (NK) cells [J ] . Seminars in Immunology , 2006 , 18 ( 3 ): 145 - 150 .

CHENG M , CHEN Y Y , XIAO W H , et al . NK cell-based immunotherapy for malignant diseases [J ] . Cellular & Molecular Immunology , 2013 , 10 ( 3 ): 230 - 252 .

LIU S Z , GALAT V , GALAT Y , et al . NK cell-based cancer immunotherapy: from basic biology to clinical development [J ] . Journal of Hematology & Oncology , 2021 , 14 ( 1 ): 7 .

FANG F , XIAO W H , TIAN Z G . Challenges of NK cell-based immunotherapy in the new era [J ] . Frontiers of Medicine , 2018 , 12 ( 4 ): 440 - 450 .

BI J C , TIAN Z G . NK cell dysfunction and checkpoint immunotherapy [J ] . Frontiers in Immunology , 2019 , 10 : 1999 .

KHAN M , AROOJ S , WANG H . NK cell-based immune checkpoint inhibition [J ] . Frontiers in Immunology , 2020 , 11 : 167 .

SUN H Y , SUN C . The rise of NK cell checkpoints as promising therapeutic targets in cancer immunotherapy [J ] . Frontiers in Immunology , 2019 , 10 : 2354 .

STERNER R C , STERNER R M . CAR-T cell therapy: Current limitations and potential strategies [J ] . Blood Cancer Journal , 2021 , 11 : 69 .

HARGADON K M , JOHNSON C E , WILLIAMS C J . Immune checkpoint blockade therapy for cancer: An overview of FDA-approved immune checkpoint inhibitors [J ] . International Immunopharmacology , 2018 , 62 : 29 - 39 .

HODGINS J J , KHAN S T , PARK M M , et al . Killers 2.0: NK cell therapies at the forefront of cancer control [J ] . The Journal of Clinical Investigation , 2019 , 129 ( 9 ): 3499 - 3510 .

BALD T , KRUMMEL M F , SMYTH M J , et al . The NK cell-cancer cycle: advances and new challenges in NK cell-based immunotherapies [J ] . Nature Immunology , 2020 , 21 ( 8 ): 835 - 847 .

HU W L , WANG G S , HUANG D S , et al . Cancer immunotherapy based on natural killer cells: current progress and new opportunities [J ] . Frontiers in Immunology , 2019 , 10 : 1205 .

RUGGERI L , CAPANNI M , URBANI E , et al . Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants [J ] . Science , 2002 , 295 ( 5562 ): 2097 - 2100 .

SAETERSMOEN M L , HAMMER Q , VALAMEHR B , et al . Off-the-shelf cell therapy with induced pluripotent stem cell-derived natural killer cells [J ] . Seminars in Immunopathology , 2019 , 41 ( 1 ): 59 - 68 .

WANG W X , JIANG J T , WU C P . CAR-NK for tumor immunotherapy: Clinical transformation and future prospects [J ] . Cancer Letters , 2020 , 472 : 175 - 180 .

LIU E L , MARIN D , BANERJEE P , et al . Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors [J ] . The New England Journal of Medicine , 2020 , 382 ( 6 ): 545 - 553 .

TOMASELLO E , BLERY M , VELY E , et al . Signaling pathways engaged by NK cell receptors: double concerto for activating receptors, inhibitory receptors and NK cells [J ] . Seminars in Immunology , 2000 , 12 ( 2 ): 139 - 147 .

VIVIER E , NUNÈS J A , VÉLY F . Natural killer cell signaling pathways [J ] . Science , 2004 , 306 ( 5701 ): 1517 - 1519 .

AFOLABI L O , ADESHAKIN A O , SANI M M , et al . Genetic reprogramming for NK cell cancer immunotherapy with CRISPR/Cas9 [J ] . Immunology , 2019 , 158 ( 2 ): 63 - 69 .

PFEFFERLE A , HUNTINGTON N D . You have got a fast CAR: chimeric antigen receptor NK cells in cancer therapy [J ] . Cancers , 2020 , 12 ( 3 ): 706 .

HU Y , TIAN Z G , ZHANG C . Chimeric antigen receptor (CAR)-transduced natural killer cells in tumor immunotherapy [J ] . Acta Pharmacologica Sinica , 2018 , 39 ( 2 ): 167 - 176 .

TÖPFER K , CARTELLIERI M , MICHEN S , et al . DAP12-based activating chimeric antigen receptor for NK cell tumor immunotherapy [J ] . Journal of Immunology (Baltimore , Md: 1950 ), 2015 , 194 ( 7 ): 3201 - 3212 .

LI Y , HERMANSON D L , MORIARITY B S , et al . Human iPSC-derived natural killer cells engineered with chimeric antigen receptors enhance anti-tumor activity [J ] . Cell Stem Cell , 2018 , 23 ( 2 ): 181 - 192.e5 .

MEHTA R S , REZVANI K . Chimeric antigen receptor expressing natural killer cells for the immunotherapy of cancer [J ] . Frontiers in Immunology , 2018 , 9 : 283 .

SHANKAR K , CAPITINI C M , SAHA K . Genome engineering of induced pluripotent stem cells to manufacture natural killer cell therapies [J ] . Stem Cell Research & Therapy , 2020 , 11 ( 1 ): 234 .

KNORR D A , NI Z Y , HERMANSON D , et al . Clinical-scale derivation of natural killer cells from human pluripotent stem cells for cancer therapy [J ] . Stem Cells Translational Medicine , 2013 , 2 ( 4 ): 274 - 283 .

SPANHOLTZ J , PREIJERS F , TORDOIR M , et al . Clinical-grade generation of active NK cells from cord blood hematopoietic progenitor cells for immunotherapy using a closed-system culture process [J ] . PLoS One , 2011 , 6 ( 6 ): e20740 .

WOLL P S , MARTIN C H , MILLER J S , et al . Human embryonic stem cell-derived NK cells acquire functional receptors and cytolytic activity [J ] . Journal of Immunology , 2005 , 175 ( 8 ): 5095 - 5103 .

IMAI C , IWAMOTO S , CAMPANA D . Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells [J ] . Blood , 2005 , 106 ( 1 ): 376 - 383 .

OYER J L , PANDEY V , IGARASHI R Y , et al . Natural killer cells stimulated with PM21 particles expand and biodistribute in vivo : clinical implications for cancer treatment [J ] . Cytotherapy , 2016 , 18 ( 5 ): 653 - 663 .

FUJISAKI H , KAKUDA H , IMAI C , et al . Replicative potential of human natural killer cells [J ] . British Journal of Haematology , 2009 , 145 ( 5 ): 606 - 613 .

LI L Y , LI W , WANG C , et al . Adoptive transfer of natural killer cells in combination with chemotherapy improves outcomes of patients with locally advanced colon carcinoma [J ] . Cytotherapy , 2018 , 20 ( 1 ): 134 - 148 .

REIM F , DOMBROWSKI Y , RITTER C , et al . Immunoselection of breast and ovarian cancer cells with trastuzumab and natural killer cells: selective escape of CD44 high /CD24 low /HER2 low breast cancer stem cells [J ] . Cancer Research , 2009 , 69 ( 20 ): 8058 - 8066 .

CHILDS R W , CARLSTEN M . Therapeutic approaches to enhance natural killer cell cytotoxicity against cancer: the force awakens [J ] . Nature Reviews Drug Discovery , 2015 , 14 ( 7 ): 487 - 498 .

MU Y X , ZHAO Y X , LI B Y , et al . A simple method for in vitro preparation of natural killer cells from cord blood [J ] . BMC Biotechnology , 2019 , 19 ( 1 ): 80 .

HENKE E , NANDIGAMA R , ERGÜN S . Extracellular matrix in the tumor microenvironment and its impact on cancer therapy [J ] . Frontiers in Molecular Biosciences , 2020 , 6 : 160 .

COOMBE D R , GANDHI N S . Heparanase: a challenging cancer drug target [J ] . Frontiers in Oncology , 2019 , 9 : 1316 .

PUTZ E M , MAYFOSH A J , KOS K , et al . NK cell heparanase controls tumor invasion and immune surveillance [J ] . The Journal of Clinical Investigation , 2017 , 127 ( 7 ): 2777 - 2788 .

GAJEWSKI T F , MENG Y , HARLIN H . Immune suppression in the tumor microenvironment [J ] . Journal of Immunotherapy , 2006 , 29 ( 3 ): 233 - 240 .

VIEL S , MARÇAIS A , GUIMARAES F S , et al . TGF-β inhibits the activation and functions of NK cells by repressing the mTOR pathway [J ] . Science Signaling , 2016 , 9 ( 415 ): ra19 .

ZAIATZ-BITTENCOURT V , FINLAY D K , GARDINER C M . Canonical TGF-β signaling pathway represses human NK cell metabolism [J ] . The Journal of Immunology , 2018 , 200 ( 12 ): 3934 - 3941 .

BURGA R A , YVON E , CHORVINSKY E , et al . Engineering the TGFβ receptor to enhance the therapeutic potential of natural killer cells as an immunotherapy for neuroblastoma [J ] . Clinical Cancer Research , 2019 , 25 ( 14 ): 4400 - 4412 .

ZHANG Q , BI J C , ZHENG X D , et al . Blockade of the checkpoint receptor TIGIT prevents NK cell exhaustion and elicits potent anti-tumor immunity [J ] . Nature Immunology , 2018 , 19 ( 7 ): 723 - 732 .

DELCONTE R B , KOLESNIK T B , DAGLEY L F , et al . CIS is a potent checkpoint in NK cell-mediated tumor immunity [J ] . Nature Immunology , 2016 , 17 ( 7 ): 816 - 824 .

DAHER M , BASAR R , GOKDEMIR E , et al . Targeting a cytokine checkpoint enhances the fitness of armored cord blood CAR-NK cells [J ] . Blood , 2021 , 137 ( 5 ): 624 - 636 .

ZHU H , BLUM R H , BERNAREGGI D , et al . Metabolic reprograming via deletion of CISH in human iPSC-derived NK cells promotes in vivo persistence and enhances anti-tumor activity [J ] . Cell Stem Cell , 2020 , 27 ( 2 ): 224 - 237 .

CANTON B , LABNO A , ENDY D . Refinement and standardization of synthetic biological parts and devices [J ] . Nature Biotechnology , 2008 , 26 ( 7 ): 787 - 793 .

ENDY D . Foundations for engineering biology [J ] . Nature , 2005 , 438 ( 7067 ): 449 - 453 .

PORTELA R M C , VOGL T , KNIELY C , et al . Synthetic core promoters as universal parts for fine-tuning expression in different yeast species [J ] . ACS Synthetic Biology , 2017 , 6 ( 3 ): 471 - 484 .

ADAMS B L . The next generation of synthetic biology chassis: moving synthetic biology from the laboratory to the field [J ] . ACS Synthetic Biology , 2016 , 5 ( 12 ): 1328 - 1330 .

SIEGLER E L , ZHU Y N , WANG P , et al . Off-the-shelf CAR-NK cells for cancer immunotherapy [J ] . Cell Stem Cell , 2018 , 23 ( 2 ): 160 - 161 .

DEPIL S , DUCHATEAU P , GRUPP S A , et al . ' Off-the-she lf ' allogeneic CAR T cells: development and challenges [J ] . Nature Reviews Drug Discovery , 2020 , 19 ( 3 ): 185 - 199 .

ZHAO L J , CAO Y J . Engineered T cell therapy for cancer in the clinic [J ] . Frontiers in Immunology , 2019 , 10 : 2250 .

LEVINE B L , MISKIN J , WONNACOTT K , et al . Global manufacturing of CAR T cell therapy [J ] . Molecular Therapy- Methods & Clinical Development , 2017 , 4 : 92 - 101 .

CHABANNON C , MFARREJ B , GUIA S , et al . Manufacturing natural killer cells as medicinal products [J ] . Frontiers in Immunology , 2016 , 7 : 504 .

WANG X Y , RIVIÈRE I . Clinical manufacturing of CAR T cells: foundation of a promising therapy [J ] . Molecular Therapy-Oncolytics , 2016 , 3 : 16015 .

ZHANG W , JORDAN K R , SCHULTE B , et al . Characterization of clinical grade CD19 chimeric antigen receptor T cells produced using automated CliniMACS Prodigy system [J ] . Drug Design, Development and Therapy , 2018 , 12 : 3343 - 3356 .

JACKSON Z , ROE A , SHARMA A A , et al . Automated manufacture of autologous CD19 CAR-T cells for treatment of non-Hodgkin lymphoma [J ] . Frontiers in Immunology , 2020 , 11 : 1941 .

COESHOTT C , VANG B , JONES M , et al . Large-scale expansion and characterization of CD3 + T-cells in the quantum ® cell expansion system [J ] . Journal of Translational Medicine , 2019 , 17 ( 1 ): 258 .

DANESHPOUR H , YOUK H . Modeling cell-cell communication for immune systems across space and time [J ] . Current Opinion in Systems Biology , 2019 , 18 : 44 - 52 .

REN X W , ZHANG L , ZHANG Y Y , et al . Insights gained from single-cell analysis of immune cells in the tumor microenvironment [J ] . Annual Review of Immunology , 2021 , 39 : 583 - 609 .

HANASH S , SCHLIEKELMAN M . Proteomic profiling of the tumor microenvironment: recent insights and the search for biomarkers [J ] . Genome Medicine , 2014 , 6 ( 2 ): 12 .

LEE J S , RUPPIN E . Multiomics prediction of response rates to therapies to inhibit programmed cell death 1 and programmed cell death 1 ligand 1 [J ] . JAMA Oncology , 2019 , 5 ( 11 ): 1614 - 1618 .

PATEL S P , KURZROCK R . PD-L1 expression as a predictive biomarker in cancer immunotherapy [J ] . Molecular Cancer Therapeutics , 2015 , 14 ( 4 ): 847 - 856 .

MORAGA I , SPANGLER J B , MENDOZA J L , et al . Synthekines are surrogate cytokine and growth factor agonists that compel signaling through non-natural receptor dimers [J ] . eLife , 2017 , 6 : e22882 .

WU T Y H . Strategies for designing synthetic immune agonists [J ] . Immunology , 2016 , 148 ( 4 ): 315 - 325 .

SCHUKUR L , GEERING B , CHARPIN-EL HAMRI G , et al . Implantable synthetic cytokine converter cells with AND-gate logic treat experimental psoriasis [J ] . Science Translational Medicine , 2015 , 7 ( 318 ): 318ra201 .

SIEGEL J P , PURI R K . Interleukin-2 toxicity [J ] . ACS Chemical Biology , 1991 , 9 ( 4 ): 694 - 704 .

KRIEG C , LÉTOURNEAU S , PANTALEO G , et al . Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2010 , 107 ( 26 ): 11906 - 11911 .

LEVIN A M , BATES D L , RING A M , et al . Exploiting a natural conformational switch to engineer an interleukin-2 ' superkine ' [J ] . Nature , 2012 , 484 ( 7395 ): 529 - 533 .

BEYER M , SCHULTZE J L . Regulatory T cells in cancer [J ] . Blood , 2006 , 108 ( 3 ): 804 - 811 .

SILVA D A , YU S , ULGE U Y , et al . De novo design of potent and selective mimics of IL-2 and IL-15 [J ] . Nature , 2019 , 565 ( 7738 ): 186 - 191 .

SINGH S , KUMAR N K , DWIWEDI P , et al . Monoclonal antibodies: a review [J ] . Current Clinical Pharmacology , 2018 , 13 ( 2 ): 85 - 99 .

LABRIJN A F , JANMAAT M L , REICHERT J M , et al . Bispecific antibodies: a mechanistic review of the pipeline [J ] . Nature Reviews Drug Discovery , 2019 , 18 ( 8 ): 585 - 608 .

LINKE R , KLEIN A , SEIMETZ D . Catumaxomab: clinical development and future directions [J ] . mAbs , 2010 , 2 ( 2 ): 129 - 136 .

ZHAO J J , SONG Y P , LIU D L . Recent advances on blinatumomab for acute lymphoblastic leukemia [J ] . Experimental Hematology & Oncology , 2019 , 8 : 28 .

YU S N , LIU Q , HAN X W , et al . Development and clinical application of anti-HER2 monoclonal and bispecific antibodies for cancer treatment [J ] . Experimental Hematology & Oncology , 2017 , 6 : 31 .

TORRES T , ROMANELLI M , CHIRICOZZI A . A revolutionary therapeutic approach for psoriasis: bispecific biological agents [J ] . Expert Opinion on Investigational Drugs , 2016 , 25 ( 7 ): 751 - 754 .

DEMAREST S J , GLASER S M . Antibody therapeutics, antibody engineering, and the merits of protein stability [J ] . Current Opinion in Drug Discovery & Development , 2008 , 11 ( 5 ): 675 - 687 .

PLÜCKTHUN A , PACK P . New protein engineering approaches to multivalent and bispecific antibody fragments [J ] . Immunotechnology , 1997 , 3 ( 2 ): 83 - 105 .

JUNE C H , SADELAIN M . Chimeric antigen receptor therapy [J ] . The New England Journal of Medicine , 2018 , 379 ( 1 ): 64 - 73 .

FIGUEROA J A , REIDY A , MIRANDOLA L , et al . Chimeric antigen receptor engineering: a right step in the evolution of adoptive cellular immunotherapy [J ] . International Reviews of Immunology , 2015 , 34 ( 2 ): 154 - 187 .

SADELAIN M , BRENTJENS R , RIVIÈRE I . The basic principles of chimeric antigen receptor design [J ] . Cancer Discovery , 2013 , 3 ( 4 ): 388 - 398 .

VITALE I , SISTIGU A , MANIC G , et al . Mutational and antigenic landscape in tumor progression and cancer immunotherapy [J ] . Trends in Cell Biology , 2019 , 29 ( 5 ): 396 - 416 .

LOEB K R , LOEB L A . Significance of multiple mutations in cancer [J ] . Carcinogenesis , 2000 , 21 ( 3 ): 379 - 385 .

JIANG T , SHI T , ZHANG H , et al . Tumor neoantigens: From basic research to clinical applications [J ] . Journal of Hematology & Oncology , 2019 , 12 ( 1 ): 93 .

ROUDKO V , GREENBAUM B , BHARDWAJ N . Computational prediction and validation of tumor-associated neoantigens [J ] . Frontiers in Immunology , 2020 , 11 : 27 .

WANG Z D , CAO Y J . Adoptive cell therapy targeting neoantigens: a frontier for cancer research [J ] . Frontiers in Immunology , 2020 , 11 : 176 .

ITO M , HIRAMATSU H , KOBAYASHI K , et al . NOD/SCID/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells [J ] . Blood , 2002 , 100 ( 9 ): 3175 - 3182 .

STROM S C , DAVILA J , GROMPE M . Chimeric mice with humanized liver: tools for the study of drug metabolism, excretion, and toxicity [J ] . Methods in Molecular Biology , 2010 , 640 : 491 - 509 .

WHITESIDE T L . The tumor microenvironment and its role in promoting tumor growth [J ] . Oncogene , 2008 , 27 ( 45 ): 5904 - 5912 .

HIDALGO M , AMANT F , BIANKIN A V , et al . Patient-derived xenograft models: an emerging platform for translational cancer research [J ] . Cancer Discovery , 2014 , 4 ( 9 ): 998 - 1013 .

MORSUT L , ROYBAL K T , XIONG X , et al . Engineering customized cell sensing and response behaviors using synthetic Notch receptors [J ] . Cell , 2016 , 164 ( 4 ): 780 - 791 .

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