Mateusz Kwitniewski

Immunotherapy: a way to improve the therapeutic outcome of photodynamic therapy?

Photodynamic therapy (PDT) is a treatment for cancer and non-cancerous lesions involving light and a sensitizing drug, a so-called photosensitizer. Photosensitizers for PDT usually accumulate in tumour tissues with some selectivity. Thus, malignant and abnormal cells can be destroyed by PDT which acts by producing singlet oxygen and possible other reactive oxygen species. However, the efficiency of PDT is often limited by shallow light penetration into tissue. In some cases one treatment modality cannot cure a patient because of treatment limitations and/or side effects. In recent years, many preclinical studies have indicated that the therapeutic outcome of PDT can be improved, doses and side effects lowered by combination with immunotherapy. Most experiments have been done with animals and cell lines. This review summarizes the current knowledge about different immunotherapeutic approaches which can be used to improve effectiveness and extend the applications of PDT in clinics.

Diamino acid derivatives of PpIX as potential photosensitizers for photodynamic therapy of squamous cell carcinoma and prostate cancer: In vitro studies

Photodynamic therapy (PDT) is an alternative treatment modality involving light activated drugs, called photosensitizers (PSs), to treat cancer and non-cancerous conditions. The search for new compounds which might become effective PSs is the major direction for PDT development. In the present work we have studied the dark toxicity, intracellular localization and photodynamic properties of four potential, water soluble, second generation PSs--PP(Arg)(2), PP(Ser)(2)Arg(2), PP(Ala)(2)Arg(2), PP(Phe)(2)Arg(2), all diamino acid derivatives of protoporphyrin IX. Human prostate cancer (DU-145) and squamous carcinoma (A431) cells were used as experimental model. Among investigated compounds PP(Ser)(2)Arg(2) exhibited the lowest dark toxicity and the highest PDT effectiveness towards both cell lines. Fluorescence microscopy revealed the time-dependent changes in intracellular localization of the PS which were related to the phototoxicity. The results show that PP(Ser)(2)Arg(2) may be a potential PS for PDT.

Metabolic-targeted therapy with dichloroacetate (DCA): a novel treatment strategy to improve the outcome of photodynamic therapy

For the first time we present data showing that metabolic targeted therapy with dichloroacetate (DCA) may improve the outcome of photodynamic therapy. This treatment modality can be easily introduced into clinical practice guidelines.

Photodynamic therapy with 5‐aminolevulinic acid and diamino acid derivatives of protoporphyrin IX reduces papillomas in mice without eliminating transformation into squamous cell carcinoma of the skin

Photodynamic therapy (PDT) is used to treat malignant and nonmalignant diseases. It is also used for cosmetological skin treatment. PDT is generally considered to have a low risk of carcinogenicity. However, instances of nonmalignant human tumors turning malignant have been linked to PDT. In this study, we used 5‐aminolevulinic (ALA) acid and 3 water soluble photosensitizers‐PP(Arg)2, PP(Ser)2Arg2, PP(Ala)2Arg2, all diamino acid derivatives of protoporphyrin IX‐to treat benign papillomas in FVB/N mice induced by 7,12‐dimethylbenz(a)anthracene (DMBA)‐12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA). Of these drugs, ALA and PP(Arg)2 were found the most efficient. PDT reduced the number of papillomas, but with increasing effectiveness of the drugs, the risk of malignant transformation of the papillomas into squamous cell carcinomas increased. The underlying mechanisms are not clear and further investigations are needed.

Photodynamic therapy with di-l-arginine protoporphyrinate on WiDr human colon adenocarcinoma xenografts in athymic nude mice

The fluorescence kinetics of a new photosensitizer for photodynamic therapy, di-l-arginine protoporphyrinate (PP(Arg)2), was studied in the skin of healthy mice. Furthermore, induction of necrosis in WiDr human colon adenocarcinoma xenografts in athymic nude mice was studied after photodynamic therapy (PDT) with PP(Arg)2. After intravenous administration of PP(Arg)2 maximal fluorescence was reached after 72h in normal mouse skin. Complete elimination of the drug from the mouse skin was not found even after 32 days. Exposure of WiDr tumours in mice to red light (λ=632nm, fluence 150J/cm(2), fluence rate 250mW/cm(2)) 24 and 72h after intravenous administration of 10mg/kg of PP(Arg)2 caused extensive tumour necrosis. Epidermal damage and infiltration of inflammatory cells was seen 24h after light exposure but not after 72h.