Combination of PDT and a DNA demethylating agent produces anti-tumor immune response in a mouse tumor model

Pawel Mroz, Michael R. Hamblin

Research output: Chapter in Book/Report/Conference proceedingConference contribution

2 Scopus citations

Abstract

Epigenetic mechanisms, which involve DNA methylation and histone modifications, result in the heritable silencing of genes without a change in their coding sequence. However, these changes must be actively maintained after each cell division rendering them a promising target for pharmacologic inhibition. DNA methyltransferase inhibitors like 5-aza-deoxycytidine (5-aza-dC) induce and/or up-regulate the expression of MAGE-type antigens in human and mice cancer cells. Photodynamic therapy (PDT) has been shown to be an effective locally ablative anti-cancer treatment that has the additional advantage of stimulating tumor-directed immune response. We studied the effects of a new therapy that combined the demethylating agent 5-aza-dC with PDT in the breast cancer model 4T1 syngenic to immunocompetent BALB/c mice. PDT was used as a locally ablating tumor treatment that is capable of eliciting strong and tumor directed immune response while 5-aza-dC pretreatment was used promote de novo induction of the expression of P1A.protein. This is the mouse homolog of human MAGE family antigens and is reported to function as a tumor rejection antigen in certain mouse tumors. This strategy led to an increase in PDT-mediated immune response and better treatment outcome. These results strongly suggest that the MAGE family antigens are important target for PDT mediated immune response but that their expression can be silenced by epigenetic mechanisms. Therefore the possibility that PDT can be combined with epigenetic strategies to elicit anti-tumor immunity in MAGE-positive tumor models is highly clinically significant and should be studied in detail.

Original languageEnglish (US)
Title of host publication12th World Congress of the International Photodynamic Association - Photodynamic Therapy
Subtitle of host publicationBack to the Future
DOIs
StatePublished - Dec 1 2009
Externally publishedYes
Event12th World Congress of the International Photodynamic Association - Photodynamic Therapy: Back to the Future - Seattle, WA, United States
Duration: Jun 11 2009Jun 15 2009

Publication series

NameProgress in Biomedical Optics and Imaging - Proceedings of SPIE
Volume7380
ISSN (Print)1605-7422

Other

Other12th World Congress of the International Photodynamic Association - Photodynamic Therapy: Back to the Future
CountryUnited States
CitySeattle, WA
Period6/11/096/15/09

Keywords

  • 5-aza-deoxycytidine
  • MAGE
  • epigenetics
  • photodynamic therapy
  • tumor antigens

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