Role of the Immune System in Mediating the Antitumor Effect of Benzophenothiazine Photodynamic Therapy

Hendrzak-Henion, Jill A.; Knisely, Terrence L.; Cincotta, Louis; Cincotta, Eric; Cincotta, Anthony H.

doi:10.1562/0031-8655(1999)069<0575:rotisi>2.3.co;2

Cited by 9 publications

(12 citation statements)

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“…The study further showed that NK responses were upregulated in CD4-deficient mice. Hendrzak-Henion et al (1999) showed that depletion of NK cells significantly reduced PDT efficacy against EMT6 tumours and suggested that the NK effects were indirect as they were unable to demonstrate direct killing of EMT6 tumour cells by NK cells. These findings, in combination with our present results, suggest that PDT-induced anti-tumour CD8…”

Section: Discussionmentioning

confidence: 99%

“…PDT enhances NK activity (Korbelik and Dougherty, 1999) and NK cells have been shown to have an indirect effect on the control of tumour growth by PDT (Hendrzak-Henion et al, 1999). To assess whether NK cells contribute to the control of distant tumours by PDT, SCID mice were depleted of NK cells using TM-b1, a monoclonal antibody specific for the IL-2 receptor b chain (IL-2Rb), which has been shown to deplete effectively NK cells (Tanaka et al, 1993).…”

Section: T Cellsmentioning

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: Discussionmentioning

confidence: 99%

Section: T Cellsmentioning

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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“…Recent studies showed that PDT of sarcomas with 2-iodo-5-ethylamino-9-diethylaminobenzo(␣)-phenothiazinium chloride 8 or FIGURE 4 -Histology of C6 tumors after PdBpheid-PDT. C6 glioma xenografts ( ϭ7 mm) in the hindleg were treated with 5 mg/kg PdBpheid and illuminated at 360 J/cm 2 .…”

Section: The Response Of Distant Metastasis To Local Pd-bpheid-pdt Ofmentioning

confidence: 99%

“…It was shown that the activation of natural killer (NK) cells and T lymphocytes by PDT, along with induction of specific anti-tumor antibodies, 7 play a major role in the curative response. 8,9 Moreover, adoptive transfer of lymphocytes, which were tumor-sensitized by photofrin-based PDT in immunocompetent mice, improved the tumor response of SCID mice to PDT. 9 In addition, it was shown that neutrophils are indispensable for successful PDT.…”

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confidence: 99%

Local photodynamic therapy (PDT) of rat C6 glioma xenografts with Pd‐bacteriopheophorbide leads to decreased metastases and increase of animal cure compared with surgery

Schreiber

Gross

Brandis

et al. 2002

Intl Journal of Cancer

106

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Photodynamic therapy (PDT), locally applied to solid C6 rat glioma tumors in the foot of CD1 nude mice, eradicated the primary tumor and also decreased the rate of groin and lung metastases. Pd-Bacteriopheophorbide (Pd-Bpheid), a novel photosensitizer synthesized in our laboratory, was used in our study. The primary lesion in the hind leg was treated by an i.v. injection of 5 mg/kg of Pd-Bpheid and immediate illumination (650 -800 nm, 360 J/cm 2 ). This protocol and the surgical amputation of the leg were compared for local and metastasis responses. Following PDT, hemorrhage, inflammation with tumor necrosis and flattening were observed and histologically verified in the photodynamically treated tumor. Whereas local tumor control rates were up to 64% following PDT, in surgically treated animals, local tumor control was absolute. The rates of metastases in the groin and the lungs were at least 12-fold lower in the photodynamically treated animals compared with untreated or surgerytreated groups. The overall cure rates after PDT or surgery were 36% and 6%, respectively, at 8 weeks. These findings suggest that local PDT with Pd-Bpheid, which acts primarily on the tumor vasculature, efficiently eradicates the solid C6 tumors. In addition, the local PDT of the primary lesion has beneficial therapeutic effects on remote C6 metastasis, which is not obtained with surgery. It is therefore suggested, that although surgery is highly efficient for the immediate removal of the primary tumor, it lacks such systemic, therapeutic effects on distant metastases. Pd-Bpheid-PDT may thus offer a potentially superior curative therapy for C6 glioma tumors in the limb by eradicating the target tumor and by reducing the rate of metastasis in the groin and lung, possibly due to innate immunity. © 2002 Wiley-Liss, Inc. Key words: photodynamic therapy; surgery; Pd-bacteriopheophorbide; C6 glioma tumor; metastasisPhotodynamic therapy (PDT) is based on the destruction of tumors by cytotoxic reactive oxygen species (ROS) produced upon local tumor illumination in patients administered with a photosensitizer. 1-3 Following health agency approval for photofrin-based PDT in many countries, this anti-cancer treatment modality entered clinical use for the local treatment of an increasing number of indications including skin, esophageal, lung, gastric, cervical and bladder cancers. 4 PDT is usually considered a local anti-tumor treatment modality. However, reports from several laboratories suggest that PDT also induces beneficial systemic effects. Following in vitro hematoporphyrin-based PDT, adhesiveness and metastatic potential decline in DHD-K12-cultured colon carcinoma cells. Moreover, intravenous or s.c. injection of these PDT-treated cells to rats resulted in a reduced number of lung metastases compared with untreated cell injection. 5,6 Although this observation may be due to local photodynamic damage, the potential beneficial effect may be viewed as systemic. Other in vivo studies showed that local PDT with various photosensitizers mediates ...

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“…Furthermore, inhibition of inflammatory responses and vasoconstriction decrease tumor response to PDT, whereas concomitant pharmacological inhibition of angiogenesis enhances the PDT response [11][12][13][14][20][21][22][23][24]. All these studies demonstrate the importance of vascular-mediated damage in obtaining an effective tumoricidal effect after in vivo PDT.…”

Section: Working Mechanism Of Pdt In Vivomentioning

confidence: 99%

Photodynamic Therapy in Oncology

Triesscheijn¹,

et al. 2006

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Photodynamic therapy (PDT) is increasingly being recognized as an attractive, alternative treatment modality for superficial cancer. Treatment consists of two relatively simple procedures: the administration of a photosensitive drug and illumination of the tumor to activate the drug. Efficacy is high for small superficial tumors and, except for temporary skin photosensitization, there are no long-term side effects if appropriate protocols are followed. Healing occurs with little or no scarring and the procedure can be repeated without cumulative toxicity. Considering the efficacy and lack of long-term toxicity of PDT, and the fact that the first treatment of cancer with PDT was done more than 100 years ago, one might expect that this treatment had already become an established therapy. However, PDT is currently offered in only a few selected centers, although it is slowly gaining acceptance as an alternative to conventional cancer therapies. Here, we show the developmental steps PDT underwent and summarize the current clinical applications. The data show that, when properly used, PDT is an effective alternative treatment option in oncology. The

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Role of the Immune System in Mediating the Antitumor Effect of Benzophenothiazine Photodynamic Therapy

Cited by 9 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

Local photodynamic therapy (PDT) of rat C6 glioma xenografts with Pd‐bacteriopheophorbide leads to decreased metastases and increase of animal cure compared with surgery

Photodynamic Therapy in Oncology

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