Abstract
BackgroundThe 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 FindingsWe 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.ConclusionUnderstanding 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.
Highlights
To destroy tumors the immune system uses cytotoxic Tlymphocytes (CTLs) that recognize tumor antigens presented by major histocompatibility complex (MHC) class I molecules on the surface of tumor cells [1]
The tumor antigens identified to date have been broadly divided into following major groups [3]: (i) antigens encoded by cancer-testis genes expressed in various tumors, but not in normal tissues, such as the mouse gene P1A and human genes of the MAGE, BAGE and GAGE families [4,5,6,7,8,9]; (ii) differentiation antigens of the melanocytic lineage, which are present on most melanomas and on normal melanocytes [9,10,11]; and (iii) antigens that result from tumor-specific mutations in genes which are expressed in all tissues or come from viruses [12,13,14,15,16]
Photodynamic therapy (PDT) produced a local response in all b-gal antigen negative CT26 wild-type (CT26WT) tumors as manifested by a marked reduction in size lasting until day 18 (Figure 2A)
Summary
To destroy tumors the immune system uses cytotoxic Tlymphocytes (CTLs) that recognize tumor antigens presented by major histocompatibility complex (MHC) class I molecules on the surface of tumor cells [1]. The molecular identity of a number of these antigens has been recently defined both in mouse and human tumors [2]. Photodynamic Therapy (PDT) uses a non-toxic dye molecule or photosensitizer (PS) that when activated by absorbed photon of light produces cytotoxic reactive oxygen species (ROS) [19]. Direct tumor killing by ROS, tumor-associated vascular damage and most notably activation of inflammatory responses make PDT an effective anti-cancer procedure [20,21]. 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
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