Page 21 - D. Cancer biology

Intracellular Antibody Therapy with Single Chain Variable Fragment
Exhibits Anti-Cancer Activity Via Regulating KRAS Signaling Pathway

Seulmee Shin, Iiseul Kwon, Yongboo Kuk, Shinyoung Kang, Youngsil Choi and Daewoong Jo
Drug Development Team, Cellivery R&D Institute, Cellivery Therapeutics, Inc., Seoul 03929, Korea

BACKGROUND AIM
The mutations of the RAS proteins, involved in cell proliferation and Although recent studies have shown an anti-cancer effect of a single
survival, create constitutively active GTP-bound forms that promote variable domain binding to activated RAS, targeting the RAS inside
cell transformation, thus, inhibiting activated RAS function has been cells remains to be a challenge. Intracellular delivery of scFv KRAS
proposed to be an effective human cancer therapy. using TSDT to target activated RAS can be an anti-cancer therapy.

METHODS
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-scFv KRAS ) was selected.
RESULTS

CONCLUSION REFERENCES Contact information
Purified aMTD-scFv KRAS recombinant proteins Chung et al. (2020) Science Advances, 6: eaba 1193 Minyong Jung
displayed high level of cell-permeability that
were aMTD dependent and maintained the Lim et al. (2013) Clinical Cancer Research, 19: 680-690 New Drug & Business Development
anti-cancer activity of scFv KRAS . This novel Lim et al. (2013) Biomaterials, 34: 6261-6271 Cellivery Therapeutics, Inc.
protein provides a gateway for anti-mutant Lim et al. (2012) Molecular Therapy, 20: 1540-1549
RAS-based human cancer therapy and jungmy@cellivery.com
suggests a new spectrum of antibody-based Jo et al (2005) Nature Medicine, 11: 892-898
drugs. Jo et al (2001) Nature Biotechnology, 19: 929-933 +82-2-3151-8900