Page 254 - ebook

[D. Medicine/Translational Research] D-11

Selective targeted delivery of doxorubicin by developing

antibody drug conjugates with anti-CD44 antibody for the

treatment of ovarian cancer stem cells

Prabhat Shrestha¹, Yook Simmyung¹*

¹Pharmacy, Keimyung University, Deagu [42601] 대구 달서구 달구벌대로 1095 (신당동, 계명대학교), Korea

Ovarian cancer (OC) is a high risk, metastatic disease often diagnosed at the late stage. Resistance to conventional
therapy is developing due to presence of cancer stem cells (CSC). One of main ovarian CSC surface markers is CD44.

The purpose of this research is to construct anti-CD44-doxorubicin (anti-CD44-DOX) conjugates using cathepsin B
cleavable valine-citrulline (VC) linker and evaluate their treatment efficacy in OC cell models. DOX was conjugated

to VC linker using amide linkage chemistry. Construction of DOX-VC linker was confirmed by Fourier transform
infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV) and nuclear magnetic resonance spectroscopy

(NMR). Anti-CD44-DOX conjugates will be constructed using cysteine linker chemistry and will be evaluated. FTIR
results demonstrated the appearance of additional characteristics peak of secondary amide confirming the

conjugation of DOX-VC linker. UV result demonstrated significant shift in peak absorbance of DOX-VC linker and
NMR study showed the disappearance of peak at 12.41 corresponding to free OH group of linker and appearance
of additional peak at 7.71 confirming the new amide bond formation. DOX was successfully conjugated to the VC

linker. This DOX-VC linker will be conjugated with CD44+ antibody to construct anti-CD44-DOX conjugates.