Cited by 201Photodynamic Therapy Research StudiesImmunotherapy and Immune ResponsesCancer Immunotherapy and Biomarkers

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Photodynamic therapy plus low-dose cyclophosphamide generates antitumor immunity in a mouse model

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Castano, Ana P., Mroz, Pawel, Wu, Mei X., Hamblin, Michael R.·2008·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0709256105PMC PMC2291083

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Abstract

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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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)
ORCID: Wu, Mei X.
Hamblin, Michael R.
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
DOI: 10.1073/pnas.0709256105
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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Photodynamic therapy plus low-dose cyclophosphamide generates antitumor immunity in a mouse model

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