A novel dual mechanism-of-action bispecific PD-1-IL-2v armed by a "βγ-only" interleukin-2 variant
Copyright © 2024 Jiang, Chen, Liu, Wang, Feng, Cai, Chang and Zhao..
Introduction: Interleukin-2 (IL-2) is one of the first cytokines to be discovered as an immune agonist for cancer immunotherapy. Biased IL-2 variants had been discovered to eliminate Treg activation or enhance the tumor specific T cell cytotoxicity. However, all the biased IL-2 variants pose the risk to overstimulate immune response at a low-dose range. Here, we introduce a novel dual-MOA bispecific PD-1-IL-2v molecule with great anti-tumor efficacy in a high dosed manner.
Methods: The novel IL-2 variant was designed by structural truncation and shuffling. The single armed bispecific PD-1-IL-2v molecule and IL-2v were studied by immune cell activations in vitro and in vivo and anti-tumor efficacy in mouse model.
Results and discussion: The IL-2 variant in this bispecific antibody only binds to IL-2Rβγ complex in a fast-on/off manner without α, β or γ single receptor binding. This IL-2v mildly activates T and NK cells without over stimulation, meanwhile it diminishes Treg activation compared to the wild type IL-2. This unique bispecific molecule with "βγ-only" IL-2v can not only "in-cis" stimulate and expand CD8 T and NK cells moderately without Treg activation, but also block the PD-1/L1 interaction at a similar dose range with monoclonal antibody.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
|---|---|
| Enthalten in: |
Frontiers in immunology - 15(2024) vom: 28., Seite 1369376 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Jiang, Yongji [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Bispecific antibody |
|---|
| Anmerkungen: |
Date Completed 22.04.2024 Date Revised 25.04.2024 published: Electronic-eCollection Citation Status MEDLINE |
|---|
| doi: |
10.3389/fimmu.2024.1369376 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM37127401X |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM37127401X | ||
| 003 | DE-627 | ||
| 005 | 20240425235338.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240419s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3389/fimmu.2024.1369376 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1386.xml |
| 035 | |a (DE-627)NLM37127401X | ||
| 035 | |a (NLM)38638426 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Jiang, Yongji |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A novel dual mechanism-of-action bispecific PD-1-IL-2v armed by a "βγ-only" interleukin-2 variant |
| 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 22.04.2024 | ||
| 500 | |a Date Revised 25.04.2024 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Jiang, Chen, Liu, Wang, Feng, Cai, Chang and Zhao. | ||
| 520 | |a Introduction: Interleukin-2 (IL-2) is one of the first cytokines to be discovered as an immune agonist for cancer immunotherapy. Biased IL-2 variants had been discovered to eliminate Treg activation or enhance the tumor specific T cell cytotoxicity. However, all the biased IL-2 variants pose the risk to overstimulate immune response at a low-dose range. Here, we introduce a novel dual-MOA bispecific PD-1-IL-2v molecule with great anti-tumor efficacy in a high dosed manner | ||
| 520 | |a Methods: The novel IL-2 variant was designed by structural truncation and shuffling. The single armed bispecific PD-1-IL-2v molecule and IL-2v were studied by immune cell activations in vitro and in vivo and anti-tumor efficacy in mouse model | ||
| 520 | |a Results and discussion: The IL-2 variant in this bispecific antibody only binds to IL-2Rβγ complex in a fast-on/off manner without α, β or γ single receptor binding. This IL-2v mildly activates T and NK cells without over stimulation, meanwhile it diminishes Treg activation compared to the wild type IL-2. This unique bispecific molecule with "βγ-only" IL-2v can not only "in-cis" stimulate and expand CD8 T and NK cells moderately without Treg activation, but also block the PD-1/L1 interaction at a similar dose range with monoclonal antibody | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a IL-2 variant | |
| 650 | 4 | |a T cell activation | |
| 650 | 4 | |a bispecific antibody | |
| 650 | 4 | |a cancer immune therapy | |
| 650 | 4 | |a cytokine | |
| 650 | 4 | |a interleukin-2 | |
| 650 | 7 | |a Interleukin-2 |2 NLM | |
| 650 | 7 | |a Programmed Cell Death 1 Receptor |2 NLM | |
| 700 | 1 | |a Chen, Chuyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Rong |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Chuan |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Lili |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Shuang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Lei |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Frontiers in immunology |d 2010 |g 15(2024) vom: 28., Seite 1369376 |w (DE-627)NLM215811453 |x 1664-3224 |7 nnns |
| 773 | 1 | 8 | |g volume:15 |g year:2024 |g day:28 |g pages:1369376 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3389/fimmu.2024.1369376 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 15 |j 2024 |b 28 |h 1369376 | ||