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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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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