PMID- 31354732
OWN - NLM
STAT- MEDLINE
DCOM- 20200604
LR  - 20211204
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 10
DP  - 2019
TI  - A Bispecific Antibody-Based Approach for Targeting Mesothelin in Triple Negative 
      Breast Cancer.
PG  - 1593
LID - 10.3389/fimmu.2019.01593 [doi]
LID - 1593
AB  - Triple negative breast cancers (TNBC) remain a major medical challenge due to 
      poor prognosis and limited treatment options. Mesothelin is a 
      glycosyl-phosphatidyl inositol-linked membrane protein with restricted normal 
      expression and high level expression in a large proportion of TNBC, thus 
      qualifying as an attractive target. Its overexpression in breast tumors has been 
      recently correlated with a decreased disease-free survival and an increase of 
      distant metastases. The objective of the study was to investigate the relevance 
      of a bispecific antibody-based immunotherapy approach through mesothelin 
      targeting and CD16 engagement using a Fab-like bispecific format (MesobsFab). 
      Using two TNBC cell lines with different level of surface mesothelin and 
      epithelial/mesenchymal phenotypes, we showed that, in vitro, MesobsFab promotes 
      the recruitment and penetration of NK cells into tumor spheroids, induces potent 
      dose-dependent cell-mediated cytotoxicity of mesothelin-positive tumor cells, 
      cytokine secretion, and decreases cell invasiveness. MesobsFab was able to induce 
      cytotoxicity in resting human peripheral blood mononuclear cells (PBMC), mainly 
      through its NK cells-mediated antibody dependent cell cytotoxicity (ADCC) 
      activity. In vivo, the anti-tumor effect of MesobsFab depends upon a threshold of 
      MSLN density on target cells. Collectively our data support mesothelin as a 
      relevant therapeutic target for the subset of TNBC that overexpresses mesothelin 
      characterized by a low overall and disease-free survival as well as the potential 
      of MesobsFab as antibody-based immunotherapeutics.
FAU - Del Bano, Joanie
AU  - Del Bano J
AD  - Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmette, CRCM, Marseille, 
      France.
FAU - Flores-Flores, Remy
AU  - Flores-Flores R
AD  - Aix Marseille Univ, CNRS, Institut de Biologie du Developpement de Marseille, 
      UMR7288, Marseille, France.
FAU - Josselin, Emmanuelle
AU  - Josselin E
AD  - Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmette, CRCM, Marseille, 
      France.
FAU - Goubard, Armelle
AU  - Goubard A
AD  - Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmette, CRCM, Marseille, 
      France.
FAU - Ganier, Laetitia
AU  - Ganier L
AD  - Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmette, CRCM, Marseille, 
      France.
FAU - Castellano, Remy
AU  - Castellano R
AD  - Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmette, CRCM, Marseille, 
      France.
FAU - Chames, Patrick
AU  - Chames P
AD  - Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmette, CRCM, Marseille, 
      France.
FAU - Baty, Daniel
AU  - Baty D
AD  - Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmette, CRCM, Marseille, 
      France.
FAU - Kerfelec, Brigitte
AU  - Kerfelec B
AD  - Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmette, CRCM, Marseille, 
      France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190710
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Antibodies, Bispecific)
RN  - 0 (Epitopes)
RN  - 0 (GPI-Linked Proteins)
RN  - 0 (MSLN protein, human)
RN  - 0 (Receptors, IgG)
RN  - J27WDC343N (Mesothelin)
SB  - IM
MH  - Antibodies, Bispecific/*therapeutic use
MH  - Antibody-Dependent Cell Cytotoxicity
MH  - Breast Neoplasms/immunology/*therapy
MH  - Cell Line, Tumor
MH  - Epitopes
MH  - Female
MH  - GPI-Linked Proteins/*immunology
MH  - Humans
MH  - Immunotherapy/*methods
MH  - Killer Cells, Natural/*immunology
MH  - Mesothelin
MH  - Receptors, IgG/*immunology
MH  - Triple Negative Breast Neoplasms/immunology/*therapy
PMC - PMC6636429
OTO - NOTNLM
OT  - bispecific antibody (bsAb)
OT  - immunotherapy
OT  - mesothelin (MSLN)
OT  - multicellular tumor spheroid model (MCTS)
OT  - natural killer cells
OT  - triple negative breast cancer (TNBC)
EDAT- 2019/07/30 06:00
MHDA- 2020/06/05 06:00
PMCR- 2019/01/01
CRDT- 2019/07/30 06:00
PHST- 2018/12/13 00:00 [received]
PHST- 2019/06/26 00:00 [accepted]
PHST- 2019/07/30 06:00 [entrez]
PHST- 2019/07/30 06:00 [pubmed]
PHST- 2020/06/05 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2019.01593 [doi]
PST - epublish
SO  - Front Immunol. 2019 Jul 10;10:1593. doi: 10.3389/fimmu.2019.01593. eCollection 
      2019.