Page 62 - D. Cancer biology
P. 62
[D. Cancer biology-45]
Development of Antibody Drug Conjugate Targeting c-Kit
and Validation of Effectiveness in Cancer
Jin-Ock Kim¹, Sang Gyu Park¹˙²˙*
¹College of Pharmacy, Ajou University, Suwon-si 16499, Republic of Korea, ²NoveltyNobility, NoveltyNobility,
Seongnam-si 13477, Republic of Korea
c-kit is a type III receptor tyrosine kinase (RTK) that mediates cell proliferation, survival and differentiation. Gene
amplification and mutations of c-kit are observed in various cancers, including gastrointestinal stromal tumor (GIST),
chronic myelogenous leukemia (CML), acute lymphocytic leukemia (AML), melanoma, acute systemic mastocytosis
(ASM), and small cell lung cancer (SCLC).
Imatinib is a first generation RTK inhibitor targeting BCR-ABL, c-kit, and PDGFR and currently using for the treatment
of various cancers. However, it has been known that 10-50% of patients receiving imatinib shows recurrence due to
activating mutation of c-kit.
In this study, we developed and characterized NN2101, a fully human monoclonal antibody with high affinity (KD
= 2.83x10-12 M) against c-kit. In addition, we generated antibody-drug conjugate (ADC) using MCC-DM1 and
examined its therapeutic efficacy in vitro and in vivo.
