A Novel Recombinant Fcγ Receptor-Targeted Survivin Combines with Chemotherapy for Efficient Cancer Treatment

Formyl peptide receptor-like 1 inhibitor (FLIPr), an Fcγ receptor (FcγR) antagonist, can be used as a carrier to guide antigen-FLIPr fusion protein to FcγR then enhances antigen-specific immune responses. Survivin, a tumor-associated antigen, is over-expressed in various types of human cancer. In th...

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Main Authors: Chiao-Chieh Wu, Chen-Yi Chiang, Shih-Jen Liu, Hsin-Wei Chen
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/9/7/806
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spelling doaj-ebb578d6ccea4eec956b9e15cbfc4d502021-07-23T13:31:45ZengMDPI AGBiomedicines2227-90592021-07-01980680610.3390/biomedicines9070806A Novel Recombinant Fcγ Receptor-Targeted Survivin Combines with Chemotherapy for Efficient Cancer TreatmentChiao-Chieh Wu0Chen-Yi Chiang1Shih-Jen Liu2Hsin-Wei Chen3National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, TaiwanFormyl peptide receptor-like 1 inhibitor (FLIPr), an Fcγ receptor (FcγR) antagonist, can be used as a carrier to guide antigen-FLIPr fusion protein to FcγR then enhances antigen-specific immune responses. Survivin, a tumor-associated antigen, is over-expressed in various types of human cancer. In this study, we demonstrate that recombinant survivin-FLIPr fusion protein (rSur-FLIPr) binds to FcγRs, and efficient uptake by dendritic cells in vivo. In addition, rSur-FLIPr alone stimulates survivin-specific immune responses, which effectively suppresses the tumor growth. The antitumor immunities are through TAP-mediated and CD8-dependent pathways. Furthermore, preexisting anti-FLIPr antibody does not abolish antitumor responses induced by rSur-FLIPr immunization. These results suggest that FLIPr is an effective antigen delivery vector and can be repeatedly used. Combination of chemotherapy with rSur-FLIPr treatment reveals a great benefit to tumor-bearing mice. Altogether, these findings suggest that rSur-FLIPr is a potential candidate for efficient cancer therapy.https://www.mdpi.com/2227-9059/9/7/806cancer vaccineFcγ receptorformyl peptide receptor-like 1 inhibitorsurvivinimmunotherapy
collection DOAJ
language English
format Article
sources DOAJ
author Chiao-Chieh Wu
Chen-Yi Chiang
Shih-Jen Liu
Hsin-Wei Chen
spellingShingle Chiao-Chieh Wu
Chen-Yi Chiang
Shih-Jen Liu
Hsin-Wei Chen
A Novel Recombinant Fcγ Receptor-Targeted Survivin Combines with Chemotherapy for Efficient Cancer Treatment
Biomedicines
cancer vaccine
Fcγ receptor
formyl peptide receptor-like 1 inhibitor
survivin
immunotherapy
author_facet Chiao-Chieh Wu
Chen-Yi Chiang
Shih-Jen Liu
Hsin-Wei Chen
author_sort Chiao-Chieh Wu
title A Novel Recombinant Fcγ Receptor-Targeted Survivin Combines with Chemotherapy for Efficient Cancer Treatment
title_short A Novel Recombinant Fcγ Receptor-Targeted Survivin Combines with Chemotherapy for Efficient Cancer Treatment
title_full A Novel Recombinant Fcγ Receptor-Targeted Survivin Combines with Chemotherapy for Efficient Cancer Treatment
title_fullStr A Novel Recombinant Fcγ Receptor-Targeted Survivin Combines with Chemotherapy for Efficient Cancer Treatment
title_full_unstemmed A Novel Recombinant Fcγ Receptor-Targeted Survivin Combines with Chemotherapy for Efficient Cancer Treatment
title_sort novel recombinant fcγ receptor-targeted survivin combines with chemotherapy for efficient cancer treatment
publisher MDPI AG
series Biomedicines
issn 2227-9059
publishDate 2021-07-01
description Formyl peptide receptor-like 1 inhibitor (FLIPr), an Fcγ receptor (FcγR) antagonist, can be used as a carrier to guide antigen-FLIPr fusion protein to FcγR then enhances antigen-specific immune responses. Survivin, a tumor-associated antigen, is over-expressed in various types of human cancer. In this study, we demonstrate that recombinant survivin-FLIPr fusion protein (rSur-FLIPr) binds to FcγRs, and efficient uptake by dendritic cells in vivo. In addition, rSur-FLIPr alone stimulates survivin-specific immune responses, which effectively suppresses the tumor growth. The antitumor immunities are through TAP-mediated and CD8-dependent pathways. Furthermore, preexisting anti-FLIPr antibody does not abolish antitumor responses induced by rSur-FLIPr immunization. These results suggest that FLIPr is an effective antigen delivery vector and can be repeatedly used. Combination of chemotherapy with rSur-FLIPr treatment reveals a great benefit to tumor-bearing mice. Altogether, these findings suggest that rSur-FLIPr is a potential candidate for efficient cancer therapy.
topic cancer vaccine
Fcγ receptor
formyl peptide receptor-like 1 inhibitor
survivin
immunotherapy
url https://www.mdpi.com/2227-9059/9/7/806
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