Page 22 - D. Cancer biology

[D. Cancer biology-16]

Intracellular antibody therapy with single chain variable

fragment exhibits anti-cancer activity via regulating KRAS

signaling pathway

Youngsil Choi¹, Seulmee Shin¹, Iiseul Kwon¹, Yongboo Kuk¹, Moonyoung Choi¹, Shinyoung Kang¹,
Daewoong Jo¹

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

The mutations of the RAS proteins, involved in cell proliferation and survival, create constitutively active GTP-bound

forms that promote cell transformation, thus, inhibiting activated RAS function has been proposed to be an effective
human cancer therapy. While recent studies have shown a substantial anti-cancer effect of a single variable region

domain which bind to activated RAS in cancerous cells harboring a RAS mutation, targeting the RAS located inside
cells remain to be a major challenge. Therapeuticmolecule systemic delivery technology (TSDT) enabled with

sequence optimized-advanced macromolecule transduction domain (aMTD) provides a solution to intracellularly
deliver single chain fragment variable region KRAS antibody. In a sequential aMTD screening steps, the best

construct for cell-permeable single chain fragment variable KRAS antibody (CP-scFvKRAS) was selected.
Subsequently, CP-scFvKRAS had potent anti-tumorigenic activities, suppressing EGF-induced KRAS-mediated

signaling pathway and cell proliferation in KRAS mutant cancer cell lines. This novel protein provides a gateway for
anti-mutant RAS-based human cancer therapy and suggests a new spectrum of antibody-based drugs.