Coated probiotic-based drug carriers for oral delivery of tumor antigens

LIN Sisi; PAN Chao; ZHANG Yifan; LIU Jinyao

doi:10.12211/2096-8280.2022-010

您当前的位置：

首页 >

文章列表页 >

Coated probiotic-based drug carriers for oral delivery of tumor antigens

Research Article | 更新时间：2025-03-20

- Coated probiotic-based drug carriers for oral delivery of tumor antigens
- Synthetic Biology Journal Vol. 3, Issue 4, Pages: 810-820(2022)
- 作者机构：
  
  1. 上海交通大学医学院附属仁济医院，上海市肿瘤研究所，上海　200011
  2. 上海交通大学医学院附属仁济医院，分子医学研究院，上海　200127
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2022-010
  CLC： R392
- Received：29 January 2022，
  
  Revised：2022-03-10，
  
  Published：31 August 2022
- 稿件说明：
移动端阅览
林思思，潘超，张一帆，刘尽尧. 基于表面涂层益生菌的肿瘤抗原口服递送系统［J］. 合成生物学， 2022， 3（4）： 810-820

LIN Sisi， PAN Chao， ZHANG Yifan， LIU Jinyao. Coated probiotic-based drug carriers for oral delivery of tumor antigens［J］. Synthetic Biology Journal， 2022， 3（4）： 810-820
林思思，潘超，张一帆，刘尽尧. 基于表面涂层益生菌的肿瘤抗原口服递送系统［J］. 合成生物学， 2022， 3（4）： 810-820 DOI： 10.12211/2096-8280.2022-010.

LIN Sisi， PAN Chao， ZHANG Yifan， LIU Jinyao. Coated probiotic-based drug carriers for oral delivery of tumor antigens［J］. Synthetic Biology Journal， 2022， 3（4）： 810-820 DOI： 10.12211/2096-8280.2022-010.

摘要

肿瘤疫苗是一种通过递送肿瘤抗原进而激活自身特异性抗肿瘤免疫的肿瘤免疫疗法。口服具有方便、简单和高效的优势。然而现有的口服肿瘤疫苗有限，并且局限于胃肠道肿瘤的治疗。这主要与缺乏先进的口服递送载体有关。本研究设计了一种酵母细胞膜包覆的益生菌应用于口服递送系统。其中，酵母细胞膜发挥益生菌和抗原保护以及肠道淋巴系统靶向的作用；益生菌发挥搭载抗原和免疫佐剂的作用。结果显示，与裸菌相比，酵母细胞膜包覆能提高益生菌的生物利用度，增强其在派氏结的富集，促进树突状细胞的活化和抗原递呈以及小鼠血浆中OVA-IgG水平。实验证明该系统能够保护益生菌和抗原免受胃肠道环境刺激并进一步向肠道淋巴系统递送抗原，激活抗肿瘤免疫。

Abstract

Cancer vaccines

as a form of cancer immunotherapy

trigger host anti-tumor immunity by delivering tumor antigens. Oral administration has the advantages of convenience

simplicity and high efficacy. However

oral tumor vaccines have been rarely reported and existing forms are solely suitable for gastrointestinal cancer. The situation is associated with lack of advanced oral delivery systems. In this study

yeast cell membrane-coated probiotics are developed as drug carriers for oral delivery of tumor antigens. Yeast cell membranes play a dual role in protecting probiotics and antigens and facilitating targeted delivery of tumor antigens to the gut lymphatic system

while probiotics serve as both immune adjuvant and antigen carrier. As a model antigen

ovalbumin (OVA) is loaded onto probiotic surface by complexing with polyethyleneimine and hyaluronic acid

via

electrostatic interaction. Subsequently

antigen-loaded probiotics are individually camouflaged with yeast membranes by physical extrusion through a porous membrane. As reflected by similar growth to uncoated probiotics

both the coating and preparation procedures have limited influences on bacterial viability. Ex

perimental results show that

compared to unmodified bacteria

yeast cell membrane coated probiotics retain their ability to grow and divide after incubation in simulated gastrointestinal environments and exhibit an improved bioavailability following oral ingestion. The presence of embedded β-glucan on yeast membranes promotes the phagocytosis by microfold cells that locate in intestinal epithelium. After oral gavage

the coating facilitates the accumulation of wrapped probiotics in Peyer's patches and then in mesenteric lymph nodes. Furthermore

the maturation of dendritic cells and corresponding antigen presentation are enhanced by coated probiotics

which induce an OVA-specific immune response as manifested by an upgraded serum level of OVA-IgG in mice after oral administration. These results demonstrate that yeast cell membrane-coated probiotics show enhanced tolerance against insults in the gastrointestinal environment and improved delivery of antigens into the gut lymphatic system

hence activating anti-tumor immunity.

关键词

Keywords

references

ZHAO T , LI C W , GE H L , et al . Glioblastoma vaccine tumor therapy research progress [J ] . Chinese Neurosurgical Journal , 2022 , 8 ( 1 ): 2 .

GOLDMAN B , DEFRANCESCO L . Erratum: the cancer vaccine roller coaster [J ] . Nature Biotechnology , 2010 , 28 ( 6 ): 624 .

BERGERON D , CHANDOK H , NIE Q , et al . RNA-Seq for the detection of gene fusions in solid tumors: development and validation of the JAX FusionSeq™ 2.0 assay [J ] . Journal of Molecular Medicine , 2022 , 100 ( 2 ): 323 - 335 .

VELA RAMIREZ J E , SHARPE L A , PEPPAS N A . Current state and challenges in developing oral vaccines [J ] . Advanced Drug Delivery Reviews , 2017 , 114 : 116 - 131 .

BITTNER B , RICHTER W , SCHMIDT J . Subcutaneous administration of biotherapeutics: an overview of current challenges and opportunities [J ] . BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy , 2018 , 32 ( 5 ): 425 - 440 .

TAKIISHI T , FENERO C I M , CÂMARA N O S . Intestinal barrier and gut microbiota: shaping our immune responses throughout life [J ] . Tissue Barriers , 2017 , 5 ( 4 ): e1373208 .

AHLMAN H , NILSSON O . The gut as the largest endocrine organ in the body [J ] . Annals of Oncology , 2001 , 12 : S63 - S68 .

PURCHASE C , PICARD J , MCDONALD R , et al . A comparison of the oral application and injection routes using the onderstepoort biological products fowl typhoid vaccine, its safety, efficacy and duration of protection in commercial laying hens [J ] . Journal of the South African Veterinary Association , 2008 , 79 ( 1 ): 39 - 43 .

KIM L , MARTINEZ C J , HODGSON K A , et al . Systemic and mucosal immune responses following oral adenoviral delivery of influenza vaccine to the human intestine by radio controlled capsule [J ] . Scientific Reports , 2016 , 6 : 37295 .

HARRELL J E , KURTZ J R , BAUER D L , et al . An outer membrane vesicle-adjuvanted oral vaccine protects against lethal, oral salmonella infection [J ] . Pathogens (Basel, Switzerland) , 2021 , 10 ( 5 ): 616 .

LEE B , KADER M A , COLGATE E R , et al . Oral rotavirus vaccine shedding as a marker of mucosal immunity [J ] . Scientific Reports , 2021 , 11 : 21760 .

FOCOSI D , MAGGI F , CASADEVALL A . Mucosal vaccines, sterilizing immunity, and the future of SARS-CoV-2 virulence [J ] . Viruses , 2022 , 14 ( 2 ): 187 .

SERRADELL M C , RUPIL L L , MARTINO R A , et al . Efficient oral vaccination by bioengineering virus-like particles with protozoan surface proteins [J ] . Nature Communications , 2019 , 10 ( 1 ): 361 .

COFFEY J W , GAIHA G D , TRAVERSO G . Oral biologic delivery: advances toward oral subunit, DNA, and mRNA vaccines and the potential for mass vaccination during pandemics [J ] . Annual Review of Pharmacology and Toxicology , 2021 , 61 : 517 - 540 .

SONG Q L , JIA J J , NIU X X , et al . An oral drug delivery system with programmed drug release and imaging properties for orthotopic colon cancer therapy [J ] . Nanoscale , 2019 , 11 ( 34 ): 15958 - 15970 .

NACIUTE M , NIEMI V , KEMP R A , et al . Lipid-encapsulated oral therapeutic peptide vaccines reduce tumour growth in an orthotopic mouse model of colorectal cancer [J ] . European Journal of Pharmaceutics and Biopharmaceutics , 2020 , 152 : 183 - 192 .

VELA RAMIREZ J E , SHARPE L A , PEPPAS N A . Current state and challenges in developing oral vaccines [J ] . Advanced Drug Delivery Reviews , 2017 , 114 : 116 - 131 .

ZHANG H M , CHEN J B . Current status and future directions of cancer immunotherapy [J ] . Journal of Cancer , 2018 , 9 ( 10 ): 1773 - 1781 .

RIDDELL S R . Progress in cancer vaccines by enhanced self-presentation [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2001 , 98 ( 16 ): 8933 - 8935 .

MABBOTT N A , DONALDSON D S , OHNO H , et al . Microfold (M) cells: Important immunosurveillance posts in the intestinal epithelium [J ] . Mucosal Immunology , 2013 , 6 ( 4 ): 666 - 677 .

KOBAYASHI N , TAKAHASHI D , TAKANO S , et al . The roles of peyer's patches and microfold cells in the gut immune system: Relevance to autoimmune diseases [J ] . Frontiers in Immunology , 2019 , 10 : 2345 .

REBOLDI A , ARNON T I , RODDA L B , et al . IgA production requires B cell interaction with subepithelial dendritic cells in Peyer's patches [J ] . Science , 2016 , 352 ( 6287 ): aaf4822 .

BELOQUI A , BRAYDEN D J , ARTURSSON P , et al . A human intestinal M-cell-like model for investigating particle, antigen and microorganism translocation [J ] . Nature Protocols , 2017 , 12 ( 7 ): 1387 - 1399 .

JANG M H , KWEON M N , IWATANI K , et al . Intestinal villous M cells: an antigen entry site in the mucosal epithelium [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2004 , 101 ( 16 ): 6110 - 6115 .

LIN S S , MUKHERJEE S , LI J J , et al . Mucosal immunity-mediated modulation of the gut microbiome by oral delivery of probiotics into Peyer's patches [J ] . Science Advances , 2021 , 7 ( 20 ): eabf0677 .

LUO M , WANG H , WANG Z H , et al . A STING-activating nanovaccine for cancer immunotherapy [J ] . Nature Nanotechnology , 2017 , 12 ( 7 ): 648 - 654 .

PERSANO S , GUEVARA M L , LI Z Q , et al . Lipopolyplex potentiates anti-tumor immunity of mRNA-based vaccination [J ] . Biomaterials , 2017 , 125 : 81 - 89 .

ZHU L B , GE F , YANG L J , et al . Alginate particles with ovalbumin (OVA) peptide can serve as a carrier and adjuvant for immune therapy in B16-OVA cancer model [J ] . Medical Science Monitor Basic Research , 2017 , 23 : 166 - 172 .

WANG L , CAO Z P , ZHANG M M , et al . Spatiotemporally controllable distribution of combination therapeutics in solid tumors by dually modified bacteria [J ] . Advanced Materials , 2022 , 34 ( 1 ): e2106669 .

PAN C , LI J J , HOU W L , et al . Polymerization-mediated multifunctionalization of living cells for enhanced cell-based therapy [J ] . Advanced Materials , 2021 , 33 ( 13 ): e2007379 .

LI J J , HOU W L , LIN S S , et al . Polydopamine nanoparticle-mediated dopaminergic immunoregulation in colitis [J ] . Advanced Science , 2022 , 9 ( 1 ): e2104006 .

WANG X Y , CAO Z P , ZHANG M M , et al . Bioinspired oral delivery of gut microbiota by self-coating with biofilms [J ] . Science Advances , 2020 , 6 ( 26 ): eabb1952 .

LIN S S , ZHANG R Q , SHEN L , et al . Alterations in the gut barrier and involvement of Toll-like receptor 4 in murine postoperative ileus [J ] . Neurogastroenterology & Motility , 2018 , 30 ( 6 ): e13286 .

SIEGEL R L , MILLER K D , FUCHS H E , et al . Cancer statistics, 2021 [J ] . CA: A Cancer Journal for Clinicians , 2021 , 71 ( 1 ): 7 - 33 .

YE Z L , QIAN Q M , JIN H J , et al . Cancer vaccine: learning lessons from immune checkpoint inhibitors [J ] . Journal of Cancer , 2018 , 9 ( 2 ): 263 - 268 .

SINGH J , BOWNE W B , SNOOK A E . Cancer vaccines and immunotherapy for tumor prevention and treatment [J ] . Vaccines , 2021 , 9 ( 11 ): 1298 .

ZHANG L , WANG W , WANG S X . Effect of vaccine administration modality on immunogenicity and efficacy [J ] . Expert Review of Vaccines , 2015 , 14 ( 11 ): 1509 - 1523 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Research on live biotherapeutic products in metabolic diseases

Advancements in the study of probiotics for adjunctive prevention and treatment of malignancies

Applications of synthetic biology in developing microbial-vectored cancer vaccines

Advances in synthetic biology assisted intestinal microecological therapy

Related Author

sisi LIN

Chao PAN

Yifan ZHANG

Jinyao LIU

WEI Tao

ZHANG Suxiu

KUANG Jiaqi

JIANG Han

Related Institution

College of Animal Science， South China Agricultural University

College of Food Science， South China Agricultural University

Biochemical Engineering College， Beijing Union University

Beijing Key Laboratory for Utilization of Biomass Wastes

Center for Cancer Immunology， Faculty of Pharmaceutical Sciences， Shenzhen Institute of Advanced Technology， Shenzhen University of Advanced Technology， Chinese Academy of Sciences （CAS）

⁰