2024.05.10
CGC-602 (project name) is a bispecific molecule with the targets of PD-1 and IL-2. The main differentiation comes from the IL-2v moiety, which not only generate a great safety profile but also empowered the bespecific molecule dual-MOAs (PD-1/L1 axis blockage and “in-cis” T cell activation at the same time). In pre-clinical studies, CGC-602 exhibited better efficacy than PD-1 mAb in the same dose and great safety as well. The IP of CGC-602 belongs to Cure Genetics (PCT/CN2023/070898). The corresponded-author is Dr. Lei Zhao, ED of Cure Genetics and the only affiliation is Cure Genetics (https://doi.org/10.3389/fimmu.2024.1369376).
Frontiers in Immunology
Link： https://doi.org/10.3389/fimmu.2024.1369376
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. Therefore, we designed an unbiased IL-2 variant which does not bind to any single IL-2 receptor but remains the affinity to complex“βγ-only” IL-2v cThis IL-2v mildly activates T and NK cells without over stimulation, meanwhile it diminishes Treg activation compared to the wild type IL-2. an 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.
The main novelty is coming from our IL-2 variant which does not bind to each single IL-2R, including IL-2Rα, IL-2Rβ and common γ, but keeps the similar binding affinity to IL-2Rβγ complex in a fast on/off manner. This IL-2v was engineered from wtIL-2 by truncation of IL-2Rα binding surface followed by β-sheet structural shuffling and circular permutation.
野生型IL-2與“魔改”後的IL-2v的受體結合模式比較
We also confirm the advantage of PD-1-IL-2v in compare with the same dose of anti-PD-1 mAb in the in vivo anti-tumor efficacy.
Summary
CGC-602 is one of the original innovation for cancer immunotherapy by Cure Genetics. We are looking forward to the opportunities for out-licensing or co-development.
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