Bibliographic Details
| Title: |
A novel dual mechanism-of-action bispecific PD-1-IL-2v armed by a 'βγ-only' interleukin-2 variant |
| Authors: |
Yongji Jiang, Chuyuan Chen, Yuan Liu, Rong Wang, Chuan Feng, Lili Cai, Shuang Chang, Lei Zhao |
| Source: |
Frontiers in Immunology, Vol 15 (2024) |
| Publisher Information: |
Frontiers Media S.A., 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Immunologic diseases. Allergy |
| Subject Terms: |
interleukin-2, cytokine, bispecific antibody, T cell activation, cancer immune therapy, IL-2 variant, Immunologic diseases. Allergy, RC581-607 |
| More Details: |
IntroductionInterleukin-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.MethodsThe 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 discussionThe 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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1664-3224 |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fimmu.2024.1369376/full; https://doaj.org/toc/1664-3224 |
| DOI: |
10.3389/fimmu.2024.1369376 |
| Access URL: |
https://doaj.org/article/2786776c7a4448c086ec2c2d8aa3a66e |
| Accession Number: |
edsdoj.2786776c7a4448c086ec2c2d8aa3a66e |
| Database: |
Directory of Open Access Journals |
