Tim3scFv-Transforming Lactobacillus Inhibits Transplanted Tumor of Renal-Cell Carcinoma

Chen Z.a,b· Zhang H.b· Hui J.c· Jiang Y.b· Huang Z.b· Chen Z.b· Zeng W.a

Author affiliations

aDepartment of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
bDepartment of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China
cDepartment of Organ Transplant, Nanfang Hospital, Southern Medical University, Guangzhou, China

Log in to MyKarger to check if you already have access to this content.

Buy FullText & PDF Unlimited re-access via MyKarger Unrestricted printing, no saving restrictions for personal use
read more

CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!

If you would like to redeem your KAB credit, please log in.

Save over 20% compared to the individual article price.

Learn more

Access via DeepDyve Unlimited fulltext viewing Of this article Organize, annotate And mark up articles Printing And downloading restrictions apply

Select

Subscribe Access to all articles of the subscribed year(s) guaranteed for 5 years Unlimited re-access via Subscriber Login or MyKarger Unrestricted printing, no saving restrictions for personal use read more

Subcription rates

Select

* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview

Abstract of Research Article

Received: February 14, 2022
Accepted: July 05, 2022
Published online: August 18, 2022

Number of Print Pages: 12
Number of Figures: 8
Number of Tables: 3

ISSN: 0042-1138 (Print)
eISSN: 1423-0399 (Online)

For additional information: https://www.karger.com/UIN

Abstract

Introduction: T-cell immunoglobulin-3 (Tim-3) antibody drugs can treat malignant renal tumors but are expensive. To overcome this limitation, Lactococcus lactis host bacteria were used to express Tim-3 single-chain antibodies. Methods: The pLAN-CTB-Tim3scFv plasmid was constructed using molecular cloning technology and transformed into Lactococcus lactis. Expression and immune activity of proteins in the transformed bacteria were analyzed using Western blotting and enzyme-linked immunosorbent assay in vitro. A mouse subcutaneously transplanted tumor model of renal adenocarcinoma was constructed. The promoting effect of transformed bacteria on mouse spleen lymphocyte activation and their inhibitory effect on transplanted tumors were analyzed. Results: Transformed L. lactis NZ-CTB-Tim3scFv and NZ-Tim3scFv were successfully constructed. CTB-Tim3scFv secreted by NZ-CTB-Tim3scFv showed immunological activity. Compared with the NZ-Tim3scFv and NZ-Vector groups, the subgroups of splenic lymphocytes in the NZ-CTB-Tim3scFv group had a higher proportion of CD3+CD4+, CD3+CD8a+, and CD3+CD69+ cells. Ki67 and CD31 expression in the NZ-CTB-Tim3scFv group was significantly reduced. Tumor volume in the NZ-CTB-Tim3scFv group increased the least. Discussion/Conclusion: Secretion of CTB-Tim3scFv promoted the proliferation and activation of spleen lymphocytes and inhibited growth, cell proliferation, and angiogenesis of tumors. The proposed method is low cost and convenient with potential to become a new immunotherapy approach for renal-cell carcinoma.

© 2022 S. Karger AG, Basel

References Driessens G, Kline J, Gajewski TF. Costimulatory and coinhibitory receptors in anti-tumor immunity. Immunol Rev. 2009;229(1):126–44. Monney L, Sabatos CA, Gaglia JL, Ryu A, Waldner H, Chernova T, et al. Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature. 2002;415(6871):536–41. Anderson AC, Anderson DE, Bregoli L, Hastings WD, Kassam N, Lei C, et al. Promotion of tissue inflammation by the immune receptor Tim-3 expressed on innate immune cells. Science. 2007;318(5853):1141–3. Zhu C, Anderson AC, Schubart A, Xiong H, Imitola J, Khoury SJ, et al. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol. 2005;6(12):1245–52. Cai C, Xu YF, Wu ZJ, Dong Q, Li MY, Olson JC, et al. Tim-3 expression represents dysfunctional tumor infiltrating T cells in renal cell carcinoma. World J Urol. 2016;34(4):561–7. Minocha A. Probiotics for preventive health. Nutr Clin Pract. 2009;24(2):227–41. Li X, Xing Y, Guo L, Lv X, Song H, Xi T. Oral immunization with recombinant Lactococcus lactis delivering a multi-epitope antigen CTB-UE attenuates Helicobacter pylori infection in mice. Pathog Dis. 2014;72(1):78–86. Sabatos CA, Chakravarti S, Cha E, Schubart A, Sánchez-Fueyo A, Zheng XX, et al. Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance. Nat Immunol. 2003;4(11):1102–10. Nakayama M, Akiba H, Takeda K, Kojima Y, Hashiguchi M, Azuma M, et al. Tim-3 mediates phagocytosis of apoptotic cells and cross-presentation. Blood. 2009;113(16):3821–30. Dudani S, Graham J, Wells JC, Bakouny Z, Pal SK, Dizman N, et al. First-line immuno-oncology combination therapies in metastatic renal-cell carcinoma: results from the international metastatic renal-cell carcinoma database consortium. Eur Urol. 2019;76(6):861–7. Nakamura T, Sasaki T, Fujimori M, Yazawa K, Kano Y, Amano J, et al. Cloned cytosine deaminase gene expression of Bifidobacterium longum and application to enzyme/pro-drug therapy of hypoxic solid tumors. Biosci Biotechnol Biochem. 2002;66(11):2362–6. Shao CW, Tian GJ, Huang YJ, Liang W, Zheng H, Wei J, et al. Thymosin alpHa-1-transformed Bifidobacterium promotes T cell proliferation and maturation in mice by oral administration. Int Immunopharmacol. 2013;15(3):646–53. Long RT, Zeng WS, Chen LY, Guo J, Lin YZ, Huang QS, et al. Bifidobacterium as an oral delivery carrier of oxyntomodulin for obesity therapy: inhibitory effects on food intake and body weight in overweight mice. Int J Obes. 2010;34(4):712–9. Yao J, Wang JY, Lai MG, Li YX, Zhu HM, Shi RY, et al. Treatment of mice with dextran sulfate sodium-induced colitis with human interleukin 10 secreted by transformed Bifidobacterium longum. Mol Pharm. 2011;8(2):488–97. Li X, Fu GF, Fan YR, Liu WH, Liu XJ, Wang JJ, et al. Bifidobacterium adolescentis as a delivery system of endostatin for cancer gene therapy: selective inhibitor of angiogenesis and hypoxic tumor growth. Cancer Gene Ther. 2003;10(2):105–11. Shigemori S, Ihara M, Sato T, Yamamoto Y, Nigar S, Ogita T, et al. Secretion of an immunoreactive single-chain variable fragment antibody against mouse interleukin 6 by Lactococcus lactis. Appl Microbiol Biotechnol. 2017;101(1):341–9. Article / Publication Details

First-Page Preview

Abstract of Research Article

Received: February 14, 2022
Accepted: July 05, 2022
Published online: August 18, 2022

Number of Print Pages: 12
Number of Figures: 8
Number of Tables: 3

ISSN: 0042-1138 (Print)
eISSN: 1423-0399 (Online)

For additional information: https://www.karger.com/UIN

Copyright / Drug Dosage / Disclaimer Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

留言 (0)

沒有登入
gif