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Photodynamic therapy plus low-dose cyclophosphamide generates antitumor immunity in a mouse model
Open accessAbstract
Photodynamic therapy (PDT) is a modality for the treatment of cancer involving excitation of nontoxic photosensitizers with harmless visible light-producing cytotoxic reactive oxygen species. PDT causes apoptosis and necrosis of tumor cells, destruction of the tumor blood supply, and activation of the immune system. The objective of this study was to compare in an animal model of metastatic cancer PDT alone and PDT combined with low-dose cyclophosphamide (CY) a treatment that has been proposed to deplete regulatory T cells (T-regs) and increase the immune response to some tumors. We used J774 tumors (a highly metastatic reticulum cell sarcoma line) and PDT with benzoporphyrin derivative monoacid ring A, verteporfin for injection (BPD; 1-mg/kg injected i.v. followed after 15 min by 150 J/cm 2 of 690-nm light). CY (50 or 150 mg/kg i.p.) was injected 48 h before light delivery. PDT alone led to tumor regressions and a survival advantage but no permanent cures were obtained. BPD–PDT in combination with low-dose CY (but not high-dose CY) led to 70% permanent cures. Low-dose CY alone gave no permanent cures but did provide a survival advantage and was shown to reduce CD4+FoxP3+ T-regs in lymph nodes, whereas high-dose CY reduced other lymphocyte classes as well. Cured animals were rechallenged with J774 cells, and the tumors were rejected in 71% of mice. Cured mice had tumor-specific T cells in spleens as determined by a 51 Cr release assay. We conclude that low-dose CY depletes T-regs and potentiates BPD–PDT, leading to tumor cures and memory immunity.
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“It is generally agreed that apart from the direct cellular cytotoxicity, two other important factors contribute to the overall PDT effect: the vascular shutdown and local inflammatory reaction [1,2,3,4].”
From Aminolevulinic Acid (ALA) as a Prodrug in Photodynamic Therapy of Cancer (2011) · cites this paper as [1]
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Metadata
- Authors
- Castano, A. P., Mroz, P., Wu, M. X., & Hamblin, M. R.
- Affiliations
- *Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114;
- Harvard University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-04-08
- Volume
- 105
- Issue
- 14
- Pages
- 5495-5500
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2291083
- OpenAlex
- W2108157005
- Cited by
- 201
- References
- 58
- Citations by year
- 2025: 4 · 2024: 7 · 2023: 15 · 2022: 12 · 2021: 18 · 2020: 13 · 2019: 17 · 2018: 10 · 2017: 10 · 2016: 7 · 2015: 14 · 2014: 18 · 2013: 8 · 2012: 10
- FWCI
- 11.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01CA083882)
- National Institute of Allergy and Infectious Diseases (R01AI050875, R01CA/AI838801)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Photodynamic Therapy Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- photodynamic therapy, cyclophosphamide, antitumor immunity, regulatory T cells, verteporfin, benzoporphyrin derivative, reticulum cell sarcoma, J774 cells, cancer immunotherapy, tumor-specific T cells, immunological memory, combination therapy, metastatic cancer
- MeSH terms
- Animals, Cyclophosphamide, Immunity, Neoplasm Metastasis, Neoplasms, Experimental, Photochemotherapy, Survival Rate, Treatment Outcome, Cell Line, Tumor, Tumor Burden, T-Lymphocytes, Regulatory, Mice
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