Antitumor immunity induced by photodynamic therapy with aluminum disulfonated phthalocyanines and laser light

Canti, Gianfranco; Lattuada, D.; Nicolin, A; Taroni, Paola; Valentini, Gianluca; Cubeddu, Rinaldo

doi:10.1097/00001813-199408000-00009

Cited by 105 publications

(59 citation statements)

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“…Other groups of animal were treated only with PDT,with NVB only propose a satisfactory explanation for this enhancement. It may be connected to the sum of the damage induced by the different modalities on the cell membranes on the vasculature by free radical and molecular oxygen and immune effector cells , as we already observed [16]. PDT may serve as a debulking treatment leaving fewer tumor cells to be killed by cytotoxic drugs and immune lymphocytes.…”

Section: Resultsmentioning

confidence: 75%

“…Furthermore some photosensitizers, shown to stimulate the hematopoiesis in treated mice, may induce cytokine or growth factors independently of light treatment [14].There are indications that the tumoricidal activity of these activated inflammatory cells makes an essential contribution to the antitumor effect of PDT [15]. We have already shown that PDT is able to induce a strong antitumor immunity in tumor bearing mice and that the lymphocytes population can play an important role in the PDT modulation of immune response [16]. PDT induced antitumor immunity has similarities to the immune reaction induced by tumor inflammation caused by bacterial vaccines or some cytokines.…”

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confidence: 99%

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Combination of photodynamic therapy + immunotherapy + chemotherapy in murine leukiemia

Canti¹,

Calastretti²,

Bevilacqua³

et al. 2010

neo

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Photodynamic therapy (PDT) is a treatment for cancer based on the photosensitization of tumor cells by photosensitive drugs and their subsequent destruction on exposure to light of particular wavelength. The combination of drug uptake in malignant tissues and selective delivery of laser-generated light provides an effective therapy with efficient tumor citotoxicity and minimal normal tissue damage. Since immune response of the host is important in the control of tumor growth and spreading, PDT is able to increase the antitumor immunity. In our laboratory we examined the antitumor effect of combination of PDT,with photoactivated M-THPC ( meta-tetrahydroxyphenylchlorin, FOSCAN, Temoporphirin), adoptive immunotherapy, with immune lymphocytes, and chemotherapy on advanced murine tumors. Mice bearing L1210 tumor were treated at day +4 with Navelbine (NVB 1mg/Kg), at day +5,+6 with PDT (0.3mg/Kg of mTHPC and 100mW/cm2 x 200'' of exposure of laser light),and at day + 7 with immune lymphocytes(IL), collected from mice pretreated with PDT(2x10 7 cells). The results show that the combination NVB + PDT + IL demonstrates a significant synergistic antitumor effect while the chemotherapy treatment with low dose of the drug is uneffective. The same positive results were obtained with the combination of Cisplatin (CDDP 0.5mg/Kg), PDT and IL, while the CDDP treatment alone is completely uneffective. In conclusion, these results suggest that it is possible to completely cure animals bearing advanced tumors, with a combined therapy, PDT + adoptive immunotherapy + low dose chemotherapy.

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Section: Resultsmentioning

confidence: 75%

mentioning

confidence: 99%

Combination of photodynamic therapy + immunotherapy + chemotherapy in murine leukiemia

Canti¹,

Calastretti²,

Bevilacqua³

et al. 2010

neo

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“…Reports have demonstrated that the production of anti-tumour immunity by curing tumours in mice either by PDT (Canti et al, 1994) or by other methods (Suzuki et al, 2003), and have shown a resistance to rechallenge by the same tumour cells that formed the primary tumour. The baseline level of immunogenicity of the EGFP expressing tumours is confirmed by the data that a rechallenge of mice whose RIF-1 EGFP tumours had been surgically removed with the same RIF-1 EGFP cells led to a significantly reduced rate of tumour growth but no outright rejection.…”

Section: Discussionmentioning

confidence: 99%

A green fluorescent protein-expressing murine tumour but not its wild-type counterpart is cured by photodynamic therapy

2006

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The ideal cancer treatment should both destroy the primary tumour and at the same time educate the immune system to recognise the tumour as foreign so that distant metastases will also be eradicated. Photodynamic therapy (PDT) involves the i.v. administration of photosensitisers followed by illumination of the tumour with red light producing reactive oxygen species that eventually cause vascular shutdown and tumour cell death by apoptosis and necrosis. Anti-tumour immunity is stimulated after PDT due to the acute inflammatory response, generation of tumour-specific antigens, and induction of heat-shock proteins. Green fluorescent protein (GFP) is used as an optical reporter to noninvasively image the progression of mouse tumours, and in addition, may act as a foreign (jellyfish) antigen. We asked whether GFP-expressing tumours could be used to monitor the response of tumour-bearing mice to PDT, and whether the tumour response differed when a nonimmunogenic tumour cell line was transduced with GFP. We injected RIF-1 or RIF-1 EGFP (stably transduced with a retroviral vector) cells in the leg of C3H/HeN mice and both the cells and tumour grew equally well. We used PDT with benzoporphyrin derivative and a short drug-light interval. There were complete cures and 100% mouse survival of RIF-1 EGFP while RIF-1 wild-type tumours all recurred. Cured mice were resistant to rechallenge with RIF-1 EGFP cells and a rechallenge with wild-type RIF-1 cells grew significantly slower. There was also slower RIF-1 EGFP rechallenge growth but no rejection when RIF-1 EGFP tumours were surgically removed. There was a low rate of PDT cure of tumours when RIF-1 cells were transduced with an empty retroviral vector. The presence of antibodies against EGFP in mouse serum suggests EGFP can act as a foreign antigen and PDT can then stimulate a long-term memory immune response.

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“…Canti and colleagues 95 examined the effects of PDT with the PS aluminium disulphonated phthalocyanine on the anti-tumour immune response in both immunosuppressed and normal mice bearing MS-2 fibrosarcomas. All mice were cured and survived indefinitely, but resistance to MS-2 rechallenge was evident only in normal surviving animals cured by PDT, whereas immunosuppressed surviving animals and animals cured by surgery died after tumour rechallenge.…”

Section: Pdt and Anti-tumour Immunitymentioning

confidence: 99%

Photodynamic therapy and anti-tumour immunity

2006

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Photodynamic therapy (PDT) uses non-toxic photosensitizers and harmless visible light in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumour microvasculature and stimulate the host immune system. In contrast to surgery, radiotherapy and chemotherapy that are mostly immunosuppressive, PDT causes acute inflammation, expression of heat-shock proteins, invasion and infiltration of the tumour by leukocytes, and might increase the presentation of tumour-derived antigens to T cells.The principle of photodynamic therapy (PDT) was first proposed over 100 years ago 1 . A recent review in Nature Reviews Cancer by Rakesh Jain and colleagues described some of the historical milestones in the development of PDT as a cancer treatment2. Many of the photosensitizers (PSs) that have been studied since PDT was first proposed are based on a porphyrin-like nucleus 3 . PSs function as catalysts when they absorb visible light and then convert molecular oxygen to a range of highly reactive oxygen species (ROS). The ROS that are produced during PDT have been shown to destroy tumours by multifactorial mechanisms4 , 5 (FIG. 1). PDT has a direct affect on cancer cells, producing cell death by necrosis and/or apoptosis 6 . PDT also has an affect on the tumour vasculature, whereby illumination and ROS production causes the shutdown of vessels and subsequently deprives the tumour of oxygen and nutrients 7,8 . Finally, PDT also has a significant effect on the immune system 9-11 , which can be either immunostimulatory or immunosuppressive.Most of the commonly used cancer therapies are immunosuppressive. Chemotherapy and ionizing radiation delivered at doses sufficient to destroy tumours are known to be toxic to the bone marrow, which is the source of all cells of the immune system, and neutropaenia and other forms of myelosuppression are often the dose-limiting toxicity of these therapies. However, it should be noted that low doses of either ionizing radiation12 , 13 or chemotherapy14 can have immunostimulatory effects, including the induction of heat-shock © 2006 Nature Publishing Group Correspondence to M.R.H. Hamblin@helix.mgh.harvard.edu. Competing interests statementThe authors declare no competing financial interests. DATABASES NIH Public Access Author ManuscriptNat Rev Cancer. Author manuscript; available in PMC 2010 September 6. Published in final edited form as:Nat Rev Cancer. 2006 July ; 6(7): 535-545. doi:10.1038/nrc1894. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript proteins 15 . Less well known is the fact that major surgery can also have an immunosuppressive effect that leads to a significant diminution of lymphocyte and natural killer (NK) cell function 16 . The ideal cancer therapy would not only destroy the primary tumour, but at the same time trigger the immune system to recognize, track down and destroy any remaining tumour cells, be they at or near the site of the primary tumour or distant microm...

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Antitumor immunity induced by photodynamic therapy with aluminum disulfonated phthalocyanines and laser light

Cited by 105 publications

References 0 publications

Combination of photodynamic therapy + immunotherapy + chemotherapy in murine leukiemia

Combination of photodynamic therapy + immunotherapy + chemotherapy in murine leukiemia

A green fluorescent protein-expressing murine tumour but not its wild-type counterpart is cured by photodynamic therapy

Photodynamic therapy and anti-tumour immunity

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