Near-infrared photoimmunotherapy is effective treatment for colorectal cancer in orthotopic nude-mouse models.
Animals
Carcinogenesis
/ drug effects
Cell Line, Tumor
Colorectal Neoplasms
/ therapy
Humans
Immunoconjugates
/ pharmacology
Immunotherapy
/ methods
Indoles
/ therapeutic use
Mice
Mice, Nude
Organosilicon Compounds
/ therapeutic use
Photosensitizing Agents
/ therapeutic use
Phototherapy
/ methods
Receptors, Cell Surface
/ immunology
Treatment Outcome
Xenograft Model Antitumor Assays
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
31
01
2020
accepted:
30
05
2020
entrez:
20
6
2020
pubmed:
20
6
2020
medline:
1
9
2020
Statut:
epublish
Résumé
Photoimmunotherapy (PIT) employs the use of a near-infrared (NIR) laser to activate an antibody conjugated to a NIR-activatable dye to induce cancer cell death. PIT has shown to be effective in a number of studies, however, there are no data on its use in colorectal cancer in an orthotopic model. Humanized anti-CEA antibody (M5A) was conjugated to NIR-activatable IRDye700DX (M5A-700). PIT was validated in vitro with a colon cancer cell-line, using a laser intensity of either 4 J/cm2, 8 J/cm2, or 16 J/cm2. Orthotopic colon cancer mouse models were established by surgical implantation of LS174T tumor fragments onto the cecum. M5A-700 was administered and PIT was performed 24 hours later using a 690 nm laser. Repeat PIT was performed after 7 days in one group. Control mice received laser treatment only. In vitro PIT demonstrated tumor cell death in a laser intensity dose-dependent fashion. In orthotopic models, control mice demonstrated persistent tumor growth. Mice that underwent PIT one time had tumor growth arrested for one week, after which re-growth occurred. The group that received repeated PIT exposure had persistent inhibition of tumor growth. PIT arrests tumor growth in colon cancer orthotopic nude-mouse models. Repeated PIT arrests colon cancer growth for a longer period of time. PIT may be a useful therapy in the future as an adjunct to surgical resection or as primary therapy to suppress tumor progression.
Sections du résumé
BACKGROUND
Photoimmunotherapy (PIT) employs the use of a near-infrared (NIR) laser to activate an antibody conjugated to a NIR-activatable dye to induce cancer cell death. PIT has shown to be effective in a number of studies, however, there are no data on its use in colorectal cancer in an orthotopic model.
METHODS
Humanized anti-CEA antibody (M5A) was conjugated to NIR-activatable IRDye700DX (M5A-700). PIT was validated in vitro with a colon cancer cell-line, using a laser intensity of either 4 J/cm2, 8 J/cm2, or 16 J/cm2. Orthotopic colon cancer mouse models were established by surgical implantation of LS174T tumor fragments onto the cecum. M5A-700 was administered and PIT was performed 24 hours later using a 690 nm laser. Repeat PIT was performed after 7 days in one group. Control mice received laser treatment only.
RESULTS
In vitro PIT demonstrated tumor cell death in a laser intensity dose-dependent fashion. In orthotopic models, control mice demonstrated persistent tumor growth. Mice that underwent PIT one time had tumor growth arrested for one week, after which re-growth occurred. The group that received repeated PIT exposure had persistent inhibition of tumor growth.
CONCLUSION
PIT arrests tumor growth in colon cancer orthotopic nude-mouse models. Repeated PIT arrests colon cancer growth for a longer period of time. PIT may be a useful therapy in the future as an adjunct to surgical resection or as primary therapy to suppress tumor progression.
Identifiants
pubmed: 32555717
doi: 10.1371/journal.pone.0234643
pii: PONE-D-20-02950
pmc: PMC7302706
doi:
Substances chimiques
IRDye700DX N-hydroxysuccinimide ester
0
Immunoconjugates
0
Indoles
0
Organosilicon Compounds
0
Photosensitizing Agents
0
Receptors, Cell Surface
0
carcinoembryonic antigen binding protein, human
0
Banques de données
figshare
['10.6084/m9.figshare.12056157']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0234643Subventions
Organisme : BLRD VA
ID : I01 BX003856
Pays : United States
Organisme : BLRD VA
ID : I01 BX004494
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA121938
Pays : United States
Déclaration de conflit d'intérêts
Drs. Hollandsworth, Bouvet, Amirfakhri and Mr. Filemoni have no competing interests. The authors have read the journal's policy and the following authors have the following competing interests: Drs. Yazaki and Molnar disclose the following information: Patent pending: NIR-conjugated tumor-specific antibodies and uses thereof, Docket 054435-8166. Dr. Hoffman is affiliated with the corporation AntiCancer Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Références
J Surg Res. 2017 Oct;218:139-143
pubmed: 28985840
J Korean Soc Coloproctol. 2011 Aug;27(4):194-201
pubmed: 21980590
PLoS One. 2015 Mar 23;10(3):e0121989
pubmed: 25799218
JAMA Surg. 2015 Sep;150(9):890-8
pubmed: 26132363
Oncotarget. 2017 May 23;8(21):35069-35075
pubmed: 28456784
Protein Eng Des Sel. 2004 May;17(5):481-9
pubmed: 15316127
Ann Surg Oncol. 2015 Dec;22 Suppl 3:S1469-74
pubmed: 25893411
Clin Colon Rectal Surg. 2009 Nov;22(4):233-41
pubmed: 21037814
J Surg Res. 2015 Jul;197(1):5-11
pubmed: 25799527
Mol Cancer Ther. 2015 Jan;14(1):141-50
pubmed: 25416790
Oncotarget. 2017 Feb 7;8(6):10425-10436
pubmed: 28060726
Semin Cancer Biol. 1999 Apr;9(2):67-81
pubmed: 10202129
Br J Cancer. 2013 Feb 19;108(3):662-7
pubmed: 23322207
Asian Pac J Cancer Prev. ;18(9):2465-2470
pubmed: 28952277
Bioconjug Chem. 2020 Jan 15;31(1):28-36
pubmed: 31479610
Acc Chem Res. 2019 Aug 20;52(8):2332-2339
pubmed: 31335117
Oncotarget. 2015 Aug 14;6(23):19747-58
pubmed: 25992770