An immunocytokine consisting of a TNFR2 agonist and TNFR2 scFv enhances the expansion of regulatory T cells through TNFR2 clustering
Copyright © 2024 Elsevier Inc. All rights reserved..
Regulatory T cells (Tregs) are lymphocytes that play a central role in peripheral immune tolerance. Tregs are promising targets for the prevention and suppression of autoimmune diseases, allergies, and graft-versus-host disease, and treatments aimed at regulating their functions are being developed. In this study, we created a new modality consisting of a protein molecule that suppressed excessive immune responses by effectively and preferentially expanding Tregs. Recent studies reported that tumor necrosis factor receptor type 2 (TNFR2) expressed on Tregs is involved in the proliferation and activation of Tregs. Therefore, we created a functional immunocytokine, named TNFR2-ICK-Ig, consisting of a fusion protein of an anti-TNFR2 single-chain Fv (scFv) and a TNFR2 agonist TNF-α mutant protein, as a new modality that strongly enhances TNFR2 signaling. The formation of agonist-receptor multimerization (TNFR2 cluster) is effective for the induction of a strong TNFR2 signal, similar to the TNFR2 signaling mechanism exhibited by membrane-bound TNF. TNFR2-ICK-Ig improved the TNFR2 signaling activity and promoted TNFR2 cluster formation compared to a TNFR2 agonist TNF-α mutant protein that did not have an immunocytokine structure. Furthermore, the Treg expansion efficiency was enhanced. TNFR2-ICK-Ig promotes its effects via scFv, which crosslinks receptors whereas the agonists transmit stimulatory signals. Therefore, this novel molecule expands Tregs via strong TNFR2 signaling by the formation of TNFR2 clustering.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:697 |
|---|---|
| Enthalten in: |
Biochemical and biophysical research communications - 697(2024) vom: 19. Feb., Seite 149498 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Inoue, Masaki [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 14.02.2024 Date Revised 14.02.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.bbrc.2024.149498 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM367527170 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM367527170 | ||
| 003 | DE-627 | ||
| 005 | 20240215232022.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240124s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.bbrc.2024.149498 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1294.xml |
| 035 | |a (DE-627)NLM367527170 | ||
| 035 | |a (NLM)38262291 | ||
| 035 | |a (PII)S0006-291X(24)00033-0 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Inoue, Masaki |e verfasserin |4 aut | |
| 245 | 1 | 3 | |a An immunocytokine consisting of a TNFR2 agonist and TNFR2 scFv enhances the expansion of regulatory T cells through TNFR2 clustering |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 14.02.2024 | ||
| 500 | |a Date Revised 14.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Elsevier Inc. All rights reserved. | ||
| 520 | |a Regulatory T cells (Tregs) are lymphocytes that play a central role in peripheral immune tolerance. Tregs are promising targets for the prevention and suppression of autoimmune diseases, allergies, and graft-versus-host disease, and treatments aimed at regulating their functions are being developed. In this study, we created a new modality consisting of a protein molecule that suppressed excessive immune responses by effectively and preferentially expanding Tregs. Recent studies reported that tumor necrosis factor receptor type 2 (TNFR2) expressed on Tregs is involved in the proliferation and activation of Tregs. Therefore, we created a functional immunocytokine, named TNFR2-ICK-Ig, consisting of a fusion protein of an anti-TNFR2 single-chain Fv (scFv) and a TNFR2 agonist TNF-α mutant protein, as a new modality that strongly enhances TNFR2 signaling. The formation of agonist-receptor multimerization (TNFR2 cluster) is effective for the induction of a strong TNFR2 signal, similar to the TNFR2 signaling mechanism exhibited by membrane-bound TNF. TNFR2-ICK-Ig improved the TNFR2 signaling activity and promoted TNFR2 cluster formation compared to a TNFR2 agonist TNF-α mutant protein that did not have an immunocytokine structure. Furthermore, the Treg expansion efficiency was enhanced. TNFR2-ICK-Ig promotes its effects via scFv, which crosslinks receptors whereas the agonists transmit stimulatory signals. Therefore, this novel molecule expands Tregs via strong TNFR2 signaling by the formation of TNFR2 clustering | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Immunocytokine | |
| 650 | 4 | |a Regulatory T cells | |
| 650 | 4 | |a TNF receptor type 2 | |
| 650 | 4 | |a Tregs | |
| 650 | 4 | |a Tumor necrosis factor (TNF)-α | |
| 650 | 7 | |a Carrier Proteins |2 NLM | |
| 650 | 7 | |a Mutant Proteins |2 NLM | |
| 650 | 7 | |a Receptors, Tumor Necrosis Factor, Type II |2 NLM | |
| 650 | 7 | |a Single-Chain Antibodies |2 NLM | |
| 650 | 7 | |a Tumor Necrosis Factor-alpha |2 NLM | |
| 700 | 1 | |a Tsuji, Yuta |e verfasserin |4 aut | |
| 700 | 1 | |a Kashiwada, Ayaka |e verfasserin |4 aut | |
| 700 | 1 | |a Yokoyama, Asahi |e verfasserin |4 aut | |
| 700 | 1 | |a Iwata, Akane |e verfasserin |4 aut | |
| 700 | 1 | |a Abe, Yasuhiro |e verfasserin |4 aut | |
| 700 | 1 | |a Kamada, Haruhiko |e verfasserin |4 aut | |
| 700 | 1 | |a Tsunoda, Shin-Ichi |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Biochemical and biophysical research communications |d 1960 |g 697(2024) vom: 19. Feb., Seite 149498 |w (DE-627)NLM000000035 |x 1090-2104 |7 nnns |
| 773 | 1 | 8 | |g volume:697 |g year:2024 |g day:19 |g month:02 |g pages:149498 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.bbrc.2024.149498 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 697 |j 2024 |b 19 |c 02 |h 149498 | ||