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1062 GI-102, a novel CD80-IgG4-IL2v3 fusion protein driving lymphocyte expansion and anti-cancer potential through regulation of immune cells in the tumor microenvironment
  1. Min Park,
  2. Kayoung Shin,
  3. Seoho Kim,
  4. Haejong Lee,
  5. Yuseong Lee,
  6. Jisoo Kim,
  7. Eunjin Lee,
  8. Sungman Oh,
  9. Kyungwha Lee,
  10. Chong Woo Park,
  11. Jihyun Kim,
  12. Young Min Oh,
  13. Wonjae Lee,
  14. Yaein Amy Shim,
  15. Young-Gyu Cho,
  16. Young Jun Koh,
  17. Kookhwan Kim and
  18. Myoung Ho Jang
  1. GI Innovation Inc., Seoul, Songpa-gu, Republic of Korea
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background Interleukin-2 (IL-2) is a pleiotropic cytokine that plays pivotal roles in the immune response. It induces the proliferation of T cells and NK cells and demonstrates therapeutic anti-tumor activity. CD80 expressed on antigen-presenting cells provides co-stimulatory signals for T cell activation and immune responses via CD28 binding. Conversely, CD80 acts as a checkpoint molecule when bound to CTLA-4. Despite the active and progressive efforts put into the development of immune checkpoint inhibitors for cancer therapy, notable unmet medical needs continue to persist. To address these challenges and provide a safe and effective immune-boosting agent, we generated a novel CD80-IgG4-IL2v3 bispecific fusion protein which allows tumor-targeted delivery of IL-2 and robust proliferation of anti-tumor effector cells.

Methods The evaluation of anti-tumor efficacy and tumor-infiltrating lymphocytes (TIL) was conducted using the EMT6 syngeneic tumor model. Analysis of peripheral lymphocyte alterations was carried out in nonhuman primates (NHP). Intra-tissue concentration analysis of GI-102 was performed utilizing the LL/2 syngeneic tumor model.

Results The N-terminal CD80 domain of GI-102 is designed to target and block CTLA-4, while the C-terminal IL-2v3 domain has no binding affinity to IL-2Rα, while maintaining the affinity towards IL-2Rβγ. In the EMT6 syngeneic mouse model, GI-102-treated group showed significantly reduced tumor volume and percent of tumor growth rate compared with other groups. The analysis of the TIL revealed that GI-102 induced a robust expansion of both CD8+ T and NK cells in tumor microenvironment (TME), relative to vehicle control and Proleukin®. However, in comparison to Proleukin®, injection of GI-102 did not lead to an expansion of Tregs population in TME compared. A similar pattern was observed in peripheral lymphocytes of NHP that were administered GI-102 and Proleukin®. Human PBMC treated with GI-102 were analyzed for cytokine release, and no increase in inflammatory cytokines associated with cytokine release syndrome was observed with GI-102. Following the injecting GI-102 into mice bearing LL/2 tumors, elevated levels of GI-102 were detected from serum, tumor and lymphoid organs, suggesting the CD80-guided distribution of the molecule towards area reach in lymphocytes.

Conclusions GI-102 is a novel anti-cancer agent that activates immune cells and modulates tumor-infiltrating lymphocytes. This potent IL-2-based bispecific fusion protein has great potential to deliver effective therapeutic outcomes for a various types of cancer. It exhibits low toxicity and does not activate Treg, further enhancing its therapeutic value as the next-generation IL-2.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See

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