PMID- 33363632
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201229
IS  - 2221-285X (Electronic)
IS  - 1818-0876 (Print)
IS  - 1818-0876 (Linking)
VI  - 15
IP  - 6
DP  - 2020 Nov
TI  - TCR-mimic antibody-drug conjugates targeting intracellular tumor-specific mutant 
      antigen KRAS G12V mutation.
PG  - 777-785
LID - 10.1016/j.ajps.2020.01.002 [doi]
AB  - Limited clinical application of antibody-drug conjugates (ADCs) targeting tumor 
      associated antigens (TAAs) is usually caused by on-target off-tumor side effect. 
      Tumor-specific mutant antigens (TSMAs) only expressed in tumor cells which are 
      ideal targets for ADCs. In addition, intracellular somatic mutant proteins can be 
      presented on the cell surface by human leukocyte antigen class I (HLA I)molecules 
      forming tumor-specific peptide/HLA I complexes. KRAS G12V mutation frequently 
      occurred in varied cancer and was verified as a promising target for cancer 
      therapy. In this study, we generated two TCR-mimic antibody-drug conjugates 
      (TCRm-ADCs), 2E8-MMAE and 2A5-MMAE, targeting KRAS G12V/HLA-A*0201 complex, which 
      mediated specific antitumor activity in vitro and in vivo without obvious 
      toxicity. Our findings are the first time validate the strategy of TCRm-ADCs 
      targeting intracellular TSMAs, which improves the safety of antibody-based drugs 
      and provides novel strategy for precision medicine in cancer therapy.
CI  - (c) 2020 Shenyang Pharmaceutical University. Published by Elsevier B.V.
FAU - Shen, Ying
AU  - Shen Y
AD  - College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
FAU - Wei, Xiaoyue
AU  - Wei X
AD  - College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
AD  - Huabo Biopharm Co., Ltd., Shanghai 201203, China.
FAU - Jin, Shijie
AU  - Jin S
AD  - College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
FAU - Wu, Yue
AU  - Wu Y
AD  - College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
FAU - Zhao, Wenbin
AU  - Zhao W
AD  - College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
FAU - Xu, Yingchun
AU  - Xu Y
AD  - College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
FAU - Pan, Liqiang
AU  - Pan L
AD  - College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
FAU - Zhou, Zhan
AU  - Zhou Z
AD  - College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
FAU - Chen, Shuqing
AU  - Chen S
AD  - College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
LA  - eng
PT  - Journal Article
DEP - 20200305
PL  - Netherlands
TA  - Asian J Pharm Sci
JT  - Asian journal of pharmaceutical sciences
JID - 101535338
PMC - PMC7750800
OTO - NOTNLM
OT  - Human leukocyte antigen class I
OT  - KRAS G12V
OT  - TCR-mimic antibody-drug conjugates
OT  - Tumor-specific mutant antigens
COIS- The authors report no conflicts of interest.
EDAT- 2020/12/29 06:00
MHDA- 2020/12/29 06:01
PMCR- 2020/03/05
CRDT- 2020/12/28 12:00
PHST- 2019/08/26 00:00 [received]
PHST- 2019/12/29 00:00 [revised]
PHST- 2020/01/22 00:00 [accepted]
PHST- 2020/12/28 12:00 [entrez]
PHST- 2020/12/29 06:00 [pubmed]
PHST- 2020/12/29 06:01 [medline]
PHST- 2020/03/05 00:00 [pmc-release]
AID - S1818-0876(19)31112-2 [pii]
AID - 10.1016/j.ajps.2020.01.002 [doi]
PST - ppublish
SO  - Asian J Pharm Sci. 2020 Nov;15(6):777-785. doi: 10.1016/j.ajps.2020.01.002. Epub 
      2020 Mar 5.