PMID- 35681020
OWN - NLM
STAT- MEDLINE
DCOM- 20221116
LR  - 20230202
IS  - 1476-5500 (Electronic)
IS  - 0929-1903 (Linking)
VI  - 29
IP  - 11
DP  - 2022 Nov
TI  - Activation of CEACAM1 with an agonistic monoclonal antibody results in inhibition 
      of melanoma cells.
PG  - 1676-1685
LID - 10.1038/s41417-022-00486-x [doi]
AB  - Inhibitory receptors (IRs), such as the carcinoembryonic antigen-related cell 
      adhesion molecule 1 (CEACAM1), are cell surface molecules expressed on both 
      normal epithelial, endothelial, and hematopoietic cells and on neoplastic cells. 
      IRs are usually used by cancer cells to inhibit immune cell functions. Thus, 
      CEACAM1 positive tumor cells can interact homophilically with CEACAM1 expressed 
      on T and NK cells to inhibit their antibody-dependent cell-mediated cytotoxicity 
      (ADCC). In this study, we investigated the effect of agonistic/activating 
      anti-CEACAM1 monoclonal antibody (mAb) on melanoma cell lines in vitro and in 
      vivo, following our hypothesis that activation of CEACAM1 on melanoma cells by 
      distinct mAbs may induce inhibition of cancer cell proliferation and/or their 
      death. To address this, we established an activating anti-CEACAM1 mAb (CCM5.01) 
      and characterized its binding to the CEACAM1 receptor. Using this mAb, we 
      assessed the expression of CEACAM1 on four different human melanoma cell lines by 
      western blot and flow cytometry and determined its effect on cell viability in 
      vitro by MTT assay. Furthermore, we evaluated the mAb mechanism of action and 
      found that binding of CEACAM1 with CCM5.01 induced SHP1 phosphorylation and p53 
      activation resulting in melanoma cell apoptosis. For in vivo studies, a xenograft 
      model of melanoma was performed by injection of Mel-14 cells subcutaneously 
      (s.c.) in SCID/Beige mice followed by intraperitoneal (i.p.) injection of CCM5.01 
      or of IgG1 isotype control every other day. CCM5.01 treated mice showed a slight 
      but not significant decrease in tumor weight in comparison to the control group. 
      Based on the obtained data, we suggest that activating CEACAM1 on melanoma cells 
      might be a promising novel approach to fight cancers expressing this IR.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.
FAU - Zaffran, Ilan
AU  - Zaffran I
AD  - Pharmacology & Experimental Therapeutics Unit, Institute for Drug Research, 
      School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, 
      Jerusalem, Israel.
FAU - Landolina, Nadine
AU  - Landolina N
AUID- ORCID: 0000-0002-6110-6146
AD  - Pharmacology & Experimental Therapeutics Unit, Institute for Drug Research, 
      School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, 
      Jerusalem, Israel.
FAU - Gaur, Pratibha
AU  - Gaur P
AD  - Pharmacology & Experimental Therapeutics Unit, Institute for Drug Research, 
      School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, 
      Jerusalem, Israel.
FAU - Rovis, Tihana Lenac
AU  - Rovis TL
AD  - Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, 
      Croatia.
FAU - Jonjic, Stipan
AU  - Jonjic S
AD  - Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, 
      Croatia.
FAU - Mandelboim, Ofer
AU  - Mandelboim O
AD  - The Lautenberg Center for General and Tumor Immunology, The Hebrew University 
      Hadassah Medical School, IMRIC, Jerusalem, Israel.
FAU - Singer, Bernhard B
AU  - Singer BB
AUID- ORCID: 0000-0002-2213-6000
AD  - Institute of Anatomy, Medical Faculty, University Duisburg-Essen, Essen, Germany.
FAU - Levi-Schaffer, Francesca
AU  - Levi-Schaffer F
AUID- ORCID: 0000-0003-0620-2810
AD  - Pharmacology & Experimental Therapeutics Unit, Institute for Drug Research, 
      School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, 
      Jerusalem, Israel. francescal@ekmd.huji.ac.il.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220609
PL  - England
TA  - Cancer Gene Ther
JT  - Cancer gene therapy
JID - 9432230
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Cell Adhesion Molecule-1)
RN  - 0 (Ceacam1 protein, mouse)
RN  - 0 (Carcinoembryonic Antigen)
SB  - IM
EIN - Cancer Gene Ther. 2023 Jun;30(6):926. PMID: 36732550
MH  - Humans
MH  - Mice
MH  - Animals
MH  - *Antibodies, Monoclonal/pharmacology
MH  - Cell Adhesion Molecule-1
MH  - Mice, SCID
MH  - Cell Line, Tumor
MH  - *Melanoma/metabolism
MH  - Carcinoembryonic Antigen/metabolism
EDAT- 2022/06/11 06:00
MHDA- 2022/11/18 06:00
CRDT- 2022/06/10 00:27
PHST- 2022/01/20 00:00 [received]
PHST- 2022/05/23 00:00 [accepted]
PHST- 2022/05/08 00:00 [revised]
PHST- 2022/06/11 06:00 [pubmed]
PHST- 2022/11/18 06:00 [medline]
PHST- 2022/06/10 00:27 [entrez]
AID - 10.1038/s41417-022-00486-x [pii]
AID - 10.1038/s41417-022-00486-x [doi]
PST - ppublish
SO  - Cancer Gene Ther. 2022 Nov;29(11):1676-1685. doi: 10.1038/s41417-022-00486-x. 
      Epub 2022 Jun 9.