Back to Search
Start Over
Near infrared photoimmunotherapy in the treatment of disseminated peritoneal ovarian cancer.
- Source :
-
Molecular cancer therapeutics [Mol Cancer Ther] 2015 Jan; Vol. 14 (1), pp. 141-50. Date of Electronic Publication: 2014 Nov 21. - Publication Year :
- 2015
-
Abstract
- Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of intravenously injected antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to near infrared (NIR) light. Herein, we evaluate the efficacy of NIR-PIT in a mouse model of disseminated peritoneal ovarian cancer. In vitro and in vivo experiments were conducted with a HER2-expressing, luciferase-expressing, ovarian cancer cell line (SKOV-luc). An antibody-photosensitizer conjugate (APC) consisting of trastuzumab and a phthalocyanine dye, IRDye-700DX, was synthesized (tra-IR700) and cells or tumors were exposed to NIR light. In vitro PIT cytotoxicity was assessed with dead staining and luciferase activity in freely growing cells and in a three-dimensional (3D) spheroid model. In vivo NIR-PIT was performed in mice with tumors implanted in the peritoneum and in the flank and these were assessed by tumor volume and/or bioluminescence. In vitro NIR-PIT-induced cytotoxicity was light dose dependent. Repeated light exposures induced complete tumor cell killing in the 3D spheroid model. In vivo the antitumor effects of NIR-PIT were confirmed by significant reductions in both tumor volume and luciferase activity in the flank model (NIR-PIT vs. control in tumor volume changes at day 10, P = 0.0001; NIR-PIT vs. control in luciferase activity at day 4, P = 0.0237), and the peritoneal model (NIR-PIT vs. control in luciferase activity at day 7, P = 0.0037). NIR-PIT provided effective cell killing in this HER2-positive model of disseminated peritoneal ovarian cancer. Thus, NIR-PIT is a promising new therapy for the treatment of disseminated peritoneal tumors.<br /> (©2014 American Association for Cancer Research.)
- Subjects :
- Animals
Cell Line, Tumor
Dose-Response Relationship, Radiation
Female
Humans
Immunoconjugates chemistry
Immunoglobulins, Intravenous administration & dosage
Immunoglobulins, Intravenous chemistry
Immunotherapy methods
Isoindoles
Mice
Mice, Nude
Neoplasm Transplantation
Trastuzumab
Antibodies, Monoclonal, Humanized chemistry
Immunoconjugates administration & dosage
Indoles chemistry
Infrared Rays therapeutic use
Ovarian Neoplasms therapy
Peritoneal Neoplasms therapy
Radiation-Sensitizing Agents chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1538-8514
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular cancer therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 25416790
- Full Text :
- https://doi.org/10.1158/1535-7163.MCT-14-0658