Page 32 - D. Cancer biology

[D. Cancer biology-24]

SOCS3 Negatively Modulates Solid Tumor Growth By

Inhibiting JAK/STAT Signaling

Sukyeong Jeong¹, Shinyoung Park¹, Jaehyeon Kim¹, Chohyun Kim¹, Mikyung Kim¹, Youngsil Choi¹,
Daewoong Jo¹˙*

¹Cellivery R&D Institute, Cellivery Therapeutics, Inc., Seoul 03929, South Korea

Loss of suppressor of cytokine signaling 3 (SOCS3) enhances the growth and survival of some solid tumors; therefore,

methods to replenish intracellular levels of the protein may provide an effective therapy against solid tumors
dependent on Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling for carcinogenesis.

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. iCP-SOCS3 significantly suppresses cancer-associated phenotypes including proliferation (80%) in lung
cancer and glioblastoma cells and migration (65%) in gastric cancer cells, and induces changes in cell cycle regulators

(p21, p27, Cyclin A1 and Cyclin E) and apoptotic marker proteins (Bax and Caspase 3) in the solid cancer cells. In
addition, iCP-SOCS3 also significantly suppresses the growth of human solid tumors in gastric- (65%), colorectal-

(79%), lung- (69%), breast-cancer (63%) and glioblastoma xenografts (78%). These results validate iCP-SOCS3 as a
selective anti-cancer agent that acts as a negative regulator of JAK/STAT signaling.