Page 31 - D. Cancer biology

SOCS3 Negatively Modulates Solid Tumor Growth
By Inhibiting JAK/STAT Signaling

Sukyeong Jeong, Shinyoung Park, Jaehyeon Kim, Chohyun Kim, Mikyung Kim, Youngsil Choi, and Daewoong Jo
SOCS3 Team, Cellivery R&D Institute, Cellivery Therapeutics, Inc., Seoul 03929, Korea

BACKGROUND AIM
Loss of suppressor of cytokine signaling 3 (SOCS3) enhances the An advanced macromolecule transduction domain (aMTD) and a
growth and survival of some solid tumors; therefore, methods to solubilization domain were utilized to develop improved cell-
replenish intracellular levels of the protein may provide an effective permeable (iCP-) SOCS3 as a protein-based biotherapeutic against
therapy against solid tumors dependent on Janus kinase/signal solid tumors including gastric-, colorectal, lung-, breast, hepatic-
transducers and activators of transcription (JAK/STAT) signaling for cancer and glioblastoma.
carcinogenesis.
METHODS

A recombinant SOCS3 protein with a sequence-optimized advanced macromolecule transduction domain (aMTD), improved cell-permeable
(iCP-) SOCS3, has been developed as a protein-based biotherapeutic against various solid tumors and the therapeutic potential of iCP-SOCS3
as anti-cancer agent for solid tumors was examined both in cultured cells and in xenograft models.

RESULTS

Figure 1. iCP-SOCS3 Shows High Solubility/Yield Figure 3. iCP-SOCS3 Suppresses Solid Tumor Growth
& High Cell-/Tissue-Permeability in Xenograft Models
A B A B
Gastric CDX (NCI-N87)

C D
Colorectal CDX (HCT116)

C

E
F
Figure 2. iCP-SOCS3 Suppresses Tumorigenic Activities
(Proliferation & Migration) of Various Cancer Cells Lung CDX (A549)
A
G H
Breast CDX (MDA-MB-231)

I J
Hepatoma CDX (Hep3B-2.1-7)
B

K L
Glioblastoma CDX (U87-MG)

CONCLUSION REFERENCES Contact information
iCP-SOCS3 significantly suppresses cancer- Chung et al. (2020) Science Advances, 6: eaba 1193 Minyong Jung
associated phenotypes and the growth of Lim et al. (2013) Clinical Cancer Research, 19: 680-690 New Drug & Business Development
human solid tumors. Overall, these results Lim et al. (2013) Biomaterials, 34: 6261-6271
validate iCP-SOCS3 as a selective anti-cancer Lim et al. (2012) Molecular Therapy, 20: 1540-1549 Cellivery Therapeutics, Inc.
agent that acts as a negative regulator of jungmy@cellivery.com
JAK/STAT signaling. Jo et al (2005) Nature Medicine, 11: 892-898
Jo et al (2001) Nature Biotechnology, 19: 929-933 +82-2-3151-8900