Modulation of hematoporphyrin derivative-sensitized phototherapy with corynebacterium parvum in murine transitional cell carcinoma

Myers, R. C.; Lau, Benjamin H.S.; Kunihira, Dale Y.; Torrey, Robert; Woolley, James L.; Tosk, Jeffrey M.

doi:10.1016/0090-4295(89)90399-3

Cited by 37 publications

(28 citation statements)

References 12 publications

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“…This is consistent with our earlier findings with the SCCVII carcinoma model, which showed that the PDT response of this poorly immunogenic tumour is enhanced by a combined treatment with glucan SPG and cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) ; both these agents stimulate macrophage activity. On the other hand, it was reported that the response of immunogenic murine tumours to PDT is augmented by the adjuvant treatment with BCG (Cho et al, 1992), Corynebacterium parvum vaccine (Myers et al, 1989) or mycobacterial cell wall extract , which are also immune stimulants acting primarily on macrophages. Together, these results raise the possibility that PDT with adjuvant macrophage-directed immunotherapy may eventually prove clinically useful for achieving improved control of solid cancers.…”

Section: Discussionmentioning

confidence: 99%

Macrophage-directed immunotherapy as adjuvant to photodynamic therapy of cancer

Korbelik

Naraparaju²,

Yamamoto³

1997

Br J Cancer

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Summary The effect of Photofrin-based photodynamic therapy (PDT) and adjuvant treatment with serum vitamin D3-binding protein-derived macrophage-activating factor (DBPMAF) was examined using a mouse SCCVII tumour model (squamous cell carcinoma). The results show that DBPMAF can markedly enhance the curative effect of PDT. The most effective DBPMAF therapy consisted of a combination of intraperitoneal and peritumoral injections (50 and 0.5 ng kg-' respectively) administered on days 0, 4, 8 and 12 after PDT. Used with a PDT treatment curative to 25% of the treated tumours, this DBPMAF regimen boosted the cures to 100%. The DBPMAF therapy alone showed no notable effect on the growth of SCCVII tumour. The PDT-induced immunosuppression, assessed by the evaluation of delayed-type contact hypersensitivity response in treated mice, was greatly reduced with the combined DBPMAF treatment. These observations suggest that the activation of macrophages in PDT-treated mice by adjuvant immunotherapy has a synergistic effect on tumour cures. As PDT not only reduces tumour burden but also induces inflammation, it is proposed that recruitment of the activated macrophages to the inflamed tumour lesions is the major factor for the complete eradication of tumours.

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Section: Discussionmentioning

confidence: 99%

Macrophage-directed immunotherapy as adjuvant to photodynamic therapy of cancer

Korbelik

Naraparaju²,

Yamamoto³

1997

Br J Cancer

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“…Myers et al 108 combined haematoporphyrin derivative (HPD)-mediated PDT with a killed preparation of Corynebacterium parvum (CP, now Propionibacterium acnes) in a mouse model of subcutaneous bladder cancer. Giving a high dose of CP after PDT was shown to have a significantly greater effect than CP treatment before PDT.…”

Section: Pdt and Microbial Adjuvantsmentioning

confidence: 99%

“…The activation of TLR pathways can induce NFκB and, consequently, the expression of several genes involved in the activation of the immune sytem that are also important for the anti-tumour immune response107. These findings gave rise to the hypothesis that combination therapy that involves the administration of immunoadjuvants (often potential TLR ligands) and different PDT regimens might prove effective.Myers et al 108 combined haematoporphyrin derivative (HPD)-mediated PDT with a killed preparation of Corynebacterium parvum (CP, now Propionibacterium acnes) in a mouse model of subcutaneous bladder cancer. Giving a high dose of CP after PDT was shown to have a significantly greater effect than CP treatment before PDT.…”

mentioning

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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“…From these reports arose the idea of a combination therapy that involves the administration of immunoadjuvants, frequently potential TLR ligands, and different PDT regimens. One of the first combinations of PDT with an immunostimulant was a study from 1989 [20] when Myers et al combined HpD-PDT with a killed preparation of Corynebacterium parvum (CP, now Propionibacterium acnes) in a mouse model of subcutaneous bladder cancer (MBT2 in C3H mice). A low dose of CP was shown to enhance the effect of PDT while PDT reduced the benefit obtained with high dose of CP.…”

Section: -Pdt Combined With Immunoadjuvantsmentioning

confidence: 99%

Combination immunotherapy and photodynamic therapy for cancer

2006

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Cancer is a leading cause of death among modern people largely due to metastatic disease. The ideal cancer treatment should target both the primary tumor and the metastases with minimal toxicity towards normal tissue. This is best accomplished by priming the body's immune system to recognize the tumor antigens so that after the primary tumor is destroyed, distant metastases will also be eradicated. Photodynamic therapy (PDT) involves the IV administration of photosensitizers followed by illumination of the tumor with red light producing reactive oxygen species leading to vascular shutdown and tumor cell death. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, generation of tumor-specific antigens, and induction of heat-shock proteins. Combination regimens using PDT and immunostimulating treatments are likely to even further enhance post-PDT immunity. These immunostimulants are likely to include products derived from pathogenic microorganisms that are effectively recognized by Toll-like receptors and lead to upregulation of transcription factors for cytokines and inflammatory mediators. The following cascade of events causes activation of macrophages, dendritic and natural killer cells. Exogenous cytokine administration can be another way to increase PDT-induced immunity as well as treatment with a low dose of cyclophosphamide that selectively reduces T-regulatory cells. Although so far these combination therapies have only been used in animal models, their use in clinical trials should receive careful consideration.

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Modulation of hematoporphyrin derivative-sensitized phototherapy with corynebacterium parvum in murine transitional cell carcinoma

Cited by 37 publications

References 12 publications

Macrophage-directed immunotherapy as adjuvant to photodynamic therapy of cancer

Macrophage-directed immunotherapy as adjuvant to photodynamic therapy of cancer

Photodynamic therapy and anti-tumour immunity

Combination immunotherapy and photodynamic therapy for cancer

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