Photodynamic Therapy of Tumors Can Lead to Development of Systemic Antigen-Specific Immune Response

Background: The mechanism by which the immune system can effectively recognize and destroy tumors is dependent on recognition of tumor antigens. The molecular identity of a number of these antigens has recently been identified and several immunotherapies have explored them as targets. Photodynam...

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Main Authors: Mroz, Pawel, Szokalska, Angelika, Wu, Mei X., Hamblin, Michael R.
Other Authors: Harvard University--MIT Division of Health Sciences and Technology
Format: Article
Language:en_US
Published: Public Library of Science 2011
Online Access:http://hdl.handle.net/1721.1/64421
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author Mroz, Pawel
Szokalska, Angelika
Wu, Mei X.
Hamblin, Michael R.
author2 Harvard University--MIT Division of Health Sciences and Technology
author_facet Harvard University--MIT Division of Health Sciences and Technology
Mroz, Pawel
Szokalska, Angelika
Wu, Mei X.
Hamblin, Michael R.
author_sort Mroz, Pawel
collection MIT
description Background: The mechanism by which the immune system can effectively recognize and destroy tumors is dependent on recognition of tumor antigens. The molecular identity of a number of these antigens has recently been identified and several immunotherapies have explored them as targets. Photodynamic therapy (PDT) is an anti-cancer modality that uses a non-toxic photosensitizer and visible light to produce cytotoxic reactive oxygen species that destroy tumors. PDT has been shown to lead to local destruction of tumors as well as to induction of anti-tumor immune response. Methodology/Principal Findings: We used a pair of equally lethal BALB/c colon adenocarcinomas, CT26 wild-type (CT26WT) and CT26.CL25 that expressed a tumor antigen, β-galactosidase (β-gal), and we treated them with vascular PDT. All mice bearing antigen-positive, but not antigen-negative tumors were cured and resistant to rechallenge. T lymphocytes isolated from cured mice were able to specifically lyse antigen positive cells and recognize the epitope derived from beta-galactosidase antigen. PDT was capable of destroying distant, untreated, established, antigen-expressing tumors in 70% of the mice. The remaining 30% escaped destruction due to loss of expression of tumor antigen. The PDT anti-tumor effects were completely abrogated in the absence of the adaptive immune response. Conclusion: Understanding the role of antigen-expression in PDT immune response may allow application of PDT in metastatic as well as localized disease. To the best of our knowledge, this is the first time that PDT has been shown to lead to systemic, antigen- specific anti-tumor immunity.
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spelling mit-1721.1/644212022-09-27T20:03:46Z Photodynamic Therapy of Tumors Can Lead to Development of Systemic Antigen-Specific Immune Response Mroz, Pawel Szokalska, Angelika Wu, Mei X. Hamblin, Michael R. Harvard University--MIT Division of Health Sciences and Technology Hamblin, Michael R. Wu, Mei X. Hamblin, Michael R. Background: The mechanism by which the immune system can effectively recognize and destroy tumors is dependent on recognition of tumor antigens. The molecular identity of a number of these antigens has recently been identified and several immunotherapies have explored them as targets. Photodynamic therapy (PDT) is an anti-cancer modality that uses a non-toxic photosensitizer and visible light to produce cytotoxic reactive oxygen species that destroy tumors. PDT has been shown to lead to local destruction of tumors as well as to induction of anti-tumor immune response. Methodology/Principal Findings: We used a pair of equally lethal BALB/c colon adenocarcinomas, CT26 wild-type (CT26WT) and CT26.CL25 that expressed a tumor antigen, β-galactosidase (β-gal), and we treated them with vascular PDT. All mice bearing antigen-positive, but not antigen-negative tumors were cured and resistant to rechallenge. T lymphocytes isolated from cured mice were able to specifically lyse antigen positive cells and recognize the epitope derived from beta-galactosidase antigen. PDT was capable of destroying distant, untreated, established, antigen-expressing tumors in 70% of the mice. The remaining 30% escaped destruction due to loss of expression of tumor antigen. The PDT anti-tumor effects were completely abrogated in the absence of the adaptive immune response. Conclusion: Understanding the role of antigen-expression in PDT immune response may allow application of PDT in metastatic as well as localized disease. To the best of our knowledge, this is the first time that PDT has been shown to lead to systemic, antigen- specific anti-tumor immunity. United States. National Cancer Institute (grant RO1CA/AI838801) United States. National Cancer Institute (grant R01AI050875) 2011-06-13T18:24:44Z 2011-06-13T18:24:44Z 2010-12 2010-08 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/64421 Mroz P, Szokalska A, Wu MX, Hamblin MR (2010) Photodynamic Therapy of Tumors Can Lead to Development of Systemic Antigen-Specific Immune Response. PLoS ONE 5(12): e15194. doi:10.1371/journal.pone.0015194 en_US http://dx.doi.org/10.1371/journal.pone.0015194 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS
spellingShingle Mroz, Pawel
Szokalska, Angelika
Wu, Mei X.
Hamblin, Michael R.
Photodynamic Therapy of Tumors Can Lead to Development of Systemic Antigen-Specific Immune Response
title Photodynamic Therapy of Tumors Can Lead to Development of Systemic Antigen-Specific Immune Response
title_full Photodynamic Therapy of Tumors Can Lead to Development of Systemic Antigen-Specific Immune Response
title_fullStr Photodynamic Therapy of Tumors Can Lead to Development of Systemic Antigen-Specific Immune Response
title_full_unstemmed Photodynamic Therapy of Tumors Can Lead to Development of Systemic Antigen-Specific Immune Response
title_short Photodynamic Therapy of Tumors Can Lead to Development of Systemic Antigen-Specific Immune Response
title_sort photodynamic therapy of tumors can lead to development of systemic antigen specific immune response
url http://hdl.handle.net/1721.1/64421
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