PMID- 28273004
OWN - NLM
STAT- MEDLINE
DCOM- 20180220
LR  - 20191210
IS  - 1942-0870 (Electronic)
IS  - 1942-0862 (Print)
IS  - 1942-0862 (Linking)
VI  - 9
IP  - 4
DP  - 2017 May/Jun
TI  - TCR-like antibody drug conjugates mediate killing of tumor cells with low 
      peptide/HLA targets.
PG  - 603-614
LID - 10.1080/19420862.2017.1302630 [doi]
AB  - The currently marketed antibody-drug conjugates (ADC) destabilize microtubule 
      assembly in cancer cells and initiate apoptosis in patients. However, few tumor 
      antigens (TA) are expressed at high densities on cancer lesions, potentially 
      minimizing the therapeutic index of current ADC regimens. The peptide/human 
      leukocyte antigen (HLA) complex can be specifically targeted by therapeutic 
      antibodies (designated T cell receptor [TCR]-like antibodies) and adequately 
      distinguish malignant cells, but has not been the focus of ADC development. We 
      analyzed the killing potential of TCR-like ADCs when cross-linked to the DNA 
      alkylating compound duocarmycin. Our data comprise proof-of-principle results 
      that TCR-like ADCs mediate potent tumor cytotoxicity, particularly under common 
      scenarios of low TA/HLA density, and support their continued development 
      alongside agents that disrupt DNA replication. Additionally, TCR-like antibody 
      ligand binding appears to play an important role in ADC functionality and should 
      be addressed during therapy development to avoid binding patterns that negate ADC 
      killing efficacy.
FAU - Lowe, Devin B
AU  - Lowe DB
AD  - a Department of Immunotherapeutics and Biotechnology , School of Pharmacy, Texas 
      Tech University Health Sciences Center , Abilene , TX , USA.
FAU - Bivens, Camille K
AU  - Bivens CK
AD  - a Department of Immunotherapeutics and Biotechnology , School of Pharmacy, Texas 
      Tech University Health Sciences Center , Abilene , TX , USA.
FAU - Mobley, Alexis S
AU  - Mobley AS
AD  - a Department of Immunotherapeutics and Biotechnology , School of Pharmacy, Texas 
      Tech University Health Sciences Center , Abilene , TX , USA.
FAU - Herrera, Christian E
AU  - Herrera CE
AD  - a Department of Immunotherapeutics and Biotechnology , School of Pharmacy, Texas 
      Tech University Health Sciences Center , Abilene , TX , USA.
FAU - McCormick, Amanda L
AU  - McCormick AL
AD  - a Department of Immunotherapeutics and Biotechnology , School of Pharmacy, Texas 
      Tech University Health Sciences Center , Abilene , TX , USA.
FAU - Wichner, Timea
AU  - Wichner T
AD  - a Department of Immunotherapeutics and Biotechnology , School of Pharmacy, Texas 
      Tech University Health Sciences Center , Abilene , TX , USA.
FAU - Sabnani, Manoj K
AU  - Sabnani MK
AD  - b Department of Biology , College of Science, University of Texas at Arlington , 
      Arlington , TX , USA.
FAU - Wood, Laurence M
AU  - Wood LM
AD  - a Department of Immunotherapeutics and Biotechnology , School of Pharmacy, Texas 
      Tech University Health Sciences Center , Abilene , TX , USA.
FAU - Weidanz, Jon A
AU  - Weidanz JA
AD  - b Department of Biology , College of Science, University of Texas at Arlington , 
      Arlington , TX , USA.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - MAbs
JT  - mAbs
JID - 101479829
RN  - 0 (Antibodies, Neoplasm)
RN  - 0 (Duocarmycins)
RN  - 0 (HLA Antigens)
RN  - 0 (Indoles)
RN  - 0 (Peptides)
RN  - 0 (Pyrrolidinones)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - PJV9990868 (duocarmycin A)
SB  - IM
MH  - Animals
MH  - Antibodies, Neoplasm/*pharmacology
MH  - Cell Line, Tumor
MH  - Drug Delivery Systems/*methods
MH  - Duocarmycins
MH  - HLA Antigens/*immunology
MH  - Humans
MH  - Indoles/*pharmacology
MH  - Mice
MH  - Neoplasms/*drug therapy/immunology/pathology
MH  - Peptides/*immunology
MH  - Pyrrolidinones/pharmacology
MH  - *Receptors, Antigen, T-Cell
PMC - PMC5419083
OTO - NOTNLM
OT  - Antibody drug conjugate
OT  - TCR-like antibody
OT  - cancer
OT  - duocarmycin
OT  - human leukocyte antigen
OT  - immunotherapy
EDAT- 2017/03/09 06:00
MHDA- 2018/02/21 06:00
PMCR- 2018/03/08
CRDT- 2017/03/09 06:00
PHST- 2017/03/09 06:00 [pubmed]
PHST- 2018/02/21 06:00 [medline]
PHST- 2017/03/09 06:00 [entrez]
PHST- 2018/03/08 00:00 [pmc-release]
AID - 1302630 [pii]
AID - 10.1080/19420862.2017.1302630 [doi]
PST - ppublish
SO  - MAbs. 2017 May/Jun;9(4):603-614. doi: 10.1080/19420862.2017.1302630.