Specific anti-tumor immune response with photodynamic therapy mediated by benzoporphyrin derivative and chlorin(e6)

Castaño, Ana P.; Gad, Faten; Zahra, Touqir; Hamblin, Michael R.

doi:10.1117/12.477654

Cited by 7 publications

(7 citation statements)

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“…The results presented here represent the first demonstration of CD8 þ T cell-dependent control of tumours growing outside the treatment field following PDT; other studies showing inhibition of tumour growth outside the PDT treatment field have not discerned the effector cell type required for control of distant tumours (Gomer et al, 1987;Blank et al, 2001;Castano et al, 2003). We also demonstrate that PDT results in increased CD8 þ T-cell infiltration into distant untreated tumours and that control of distant tumours is tumour specific.…”

Section: Discussionsupporting

confidence: 47%

“…To address this hypothesis the effect of PDT treatment of s.c. tumours on the growth of established lung tumours in immuno-competent mice bearing concomitant s.c. and lung tumours was examined. Previous studies that have examined the effect of local PDT on distant tumours have done so in the absence of an intact immune system (Schreiber et al, 2002), were unable to detect control of distant disease (van Duijnhoven et al, 2003), performed PDT before establishment of distant tumours (Momma et al, 1998), or have not discerned a mechanism by which PDT inhibits the growth of tumours outside the treatment field (Gomer et al, 1987;Blank et al, 2001;Castano et al, 2003). In the current study, we demonstrate that control of the growth of tumours present outside the treatment field is dependent upon an intact immune system, is mediated by CD8 þ T cells and is accompanied by induction of anti-tumour immune memory responses.…”

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confidence: 99%

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CD8+ T cell-mediated control of distant tumours following local photodynamic therapy is independent of CD4+ T cells and dependent on natural killer cells

et al. 2007

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Cancer survival rates decrease in the presence of disseminated disease. However, there are few therapies that are effective at eliminating the primary tumour while providing control of distant stage disease. Photodynamic therapy (PDT) is an FDA-approved modality that rapidly eliminates local tumours, resulting in cure of early disease and palliation of advanced disease. Numerous preclinical studies have shown that local PDT treatment of tumours enhances anti-tumour immunity. We hypothesised that enhancement of a systemic anti-tumour immune response might control the growth of tumours present outside the treatment field. To test this hypothesis we delivered PDT to subcutaneous (s.c.) tumours of mice bearing both s.c. and lung tumours and monitored the growth of the untreated lung tumours. Our results demonstrate that PDT of murine tumours provided durable inhibition of the growth of untreated lung tumours. The inhibition of the growth of tumours outside the treatment field was tumour-specific and dependent on the presence of CD8 þ T cells. This inhibition was accompanied by an increase in splenic anti-tumour cytolytic activity and by an increase in CD8 þ T cell infiltration into untreated tumours. Local PDT treatment led to enhanced anti-tumour immune memory that was evident 40 days after tumour treatment and was independent of CD4 þ T cells. CD8 þ T cell control of the growth of lung tumours present outside the treatment field following PDT was dependent upon the presence of natural killer (NK) cells. These results suggest that local PDT treatment of tumours lead to induction of an anti-tumour immune response capable of controlling the growth of tumours outside the treatment field and indicate that this modality has potential in the treatment of distant stage disease.

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Section: Discussionsupporting

confidence: 47%

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confidence: 99%

CD8+ T cell-mediated control of distant tumours following local photodynamic therapy is independent of CD4+ T cells and dependent on natural killer cells

et al. 2007

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“…Previous studies that examined the effect of local PDT on distant tumors did so in the absence of an intact immune system [30], were unable to detect the control of distant disease [31], performed PDT prior to establishment of distant tumors [32], or did not discerned a mechanism by which PDT inhibits the growth of tumors outside the treatment field [33–35]. We demonstrated that control of the growth of tumors present outside the treatment field was dependent upon an intact immune system, was mediated by CD8 + cells and was accompanied by the induction of anti-tumor immunity [36].…”

Section: Pdt Enhancement Of Anti-tumor Immunitymentioning

confidence: 99%

Enhancement of anti-tumor immunity by photodynamic therapy

2009

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Photodynamic therapy (PDT) is an FDA-approved modality that rapidly eliminates local tumors, resulting in cure of early disease and palliation of advanced disease. PDT was originally considered to be a local treatment; however, both pre-clinical and clinical studies have shown that local PDT treatment of tumors can enhance systemic anti-tumor immunity. The current state of investigations into the ability of PDT to enhance anti-tumor immunity, the mechanisms behind this enhancement and the future of PDT as an immunotherapy are addressed in this review. KeywordsPDT; Neutrophil; Vaccine; T cell Photodynamic therapyPhotodynamic therapy (PDT) is an anti-tumor modality that is approved for clinical use in a number of countries, including the US, for the elimination of early-stage malignancies and the palliation of symptoms in patients with late stage tumors [1,2]. The treatment involves the systemic or topical application of a photoreactive drug known as a photosensitizer, which is inert until activated by the light of a specific wavelength [3]. Photosensitizers generally localize within cellular organelles including mitochondria and lysosomes and have some selectivity for tumor cells; however, selectivity is generally achieved by directed light delivery. Directed light delivery is obtained by placement of optical fibers at the tumor site. Light activation of the of the photosensitizer leads to the production of reactive oxygen species and direct tumor cell death.The first photosensitizer approved for clinical use in the US was Photofrin ® or Porfimer sodium, which was discovered and developed at Roswell Park Cancer Institute. Photofrin-PDT is approved by the FDA for the treatment of early and late stage non-small-cell lung carcinoma and the treatment of high-grade dysplasia associated with Barrett's esophagus [2,4]. Since the discovery and approval of Porfimer sodium, a number of second generation photosensitizers, which have increased tumor selectivity and reduced normal tissue phototoxicity, have been developed and are currently in clinical trials [1,2,5].Tumor destruction by PDT is not only a result of direct tumor destruction via generation of reactive oxygen. PDT also induces secondary events including microvascular disruption and Correspondence to: Sandra O. Gollnick, Sandra.gollnick@roswellpark.org. The local acute inflammatory response to PDT is characterized by increased expression of several pro-inflammatory cytokines, including IL-1β, , adhesion molecules E-selectin and ICAM-1 [9] and rapid leukocyte infiltration into the treated tumor site [11][12][13][14]. The initial infiltrating leukocyte population was identified as CD11b + Gr1 Hi and classified as neutrophils. Depletion of Gr1-expressing cells resulted in diminished long-term tumor growth control by PDT [12,[14][15][16], leading to the hypothesis that neutrophils are critical to PDT outcome. Recently, however, characterization of cell populations have revealed that multiple leukocyte populations express Gr1, including neutrophils, inflammator...

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“…However preclinical studies have shown that local PDT treatment of tumors can result in wide-spread systemic effects that include induction of systemic neutrophilia (6), induction of acute phase proteins (6, 7), increased circulating levels of complement proteins (8) and systemic release of pro-inflammatory cytokines (7, 9–13), all of which indicate the presence of a systemic inflammatory response. Subsequent studies showed that local PDT treatment of murine tumors results in resistance to subsequent tumor challenge (reviewed in (14, 15)) and in some cases an increased ability to control tumor growth outside the local treatment field (16, 17) that was dependent upon the presence of an intact immune response (17). The general conclusion from these pre-clinical studies was that PDT leads to the enhancement of anti-tumor immunity.…”

Section: Introductionmentioning

confidence: 99%

Enhanced Systemic Immune Reactivity to a Basal Cell Carcinoma Associated Antigen Following Photodynamic Therapy

Kabingu¹,

Oseroff²,

Wilding

et al. 2009

Clinical Cancer Research

113

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Purpose: Numerous preclinical studies have shown that local photodynamic therapy (PDT) of tumors enhances systemic antitumor immunity. However, other than single-case and anecdotal reports, this phenomenon has not been examined following clinical PDT. To determine whether PDT in a clinical setting enhances systemic recognition of tumor cells, we examined whether PDTof basal cell carcinoma resulted in an increased systemic immune response to Hip1, a tumor antigen associated with basal cell carcinoma. Experimental Design: Basal cell carcinoma lesions were either treated with PDT or surgically removed. Blood was collected from patients immediately before or 7 to 10 days following treatment. Peripheral blood leukocytes were isolated from HLA-A2^expressing patients and reactivity to a HLA-A2^restricted Hip1peptide was measured by INF-g ELISpot assay.Results: Immune recognition of Hip1 increased in patients whose basal cell carcinoma lesions were treated with PDT. This increase in reactivity was significantly greater than reactivity observed in patients whose lesions were surgically removed. Patients with superficial lesions exhibited greater enhancement of reactivity compared with patients with nodular lesions. Immune reactivity following PDTwas inversely correlated with treatment area and light dose. Conclusions: These findings show for the first time that local tumor PDTcan enhance systemic immune responses to tumors in patients, and validate previous preclinical findings.

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Specific anti-tumor immune response with photodynamic therapy mediated by benzoporphyrin derivative and chlorin(e6)

Cited by 7 publications

References 0 publications

CD8+ T cell-mediated control of distant tumours following local photodynamic therapy is independent of CD4+ T cells and dependent on natural killer cells

CD8+ T cell-mediated control of distant tumours following local photodynamic therapy is independent of CD4+ T cells and dependent on natural killer cells

Enhancement of anti-tumor immunity by photodynamic therapy

Enhanced Systemic Immune Reactivity to a Basal Cell Carcinoma Associated Antigen Following Photodynamic Therapy

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