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. 2000 Mar 21;82(8):1485–1491. doi: 10.1054/bjoc.1999.1078

Potentiation of the anti-tumour effects of Photofrin®-based photodynamic therapy by localized treatment with G-CSF

J Golab 1, G Wilczynski 2, R Zagozdzon 1,3, T Stoklosa 1, A Dabrowska 1, J Rybczynska 4, M Wasik 4, E Machaj 5, T Oldak 6, K Kozar 1, R Kaminski 1, A Giermasz 1, A Czajka 1, W Lasek 1, W Feleszko 1, M Jakobisiak 1
PMCID: PMC2363378  PMID: 10780531

Abstract

Photofrin®-based photodynamic therapy (PDT) has recently been approved for palliative and curative purposes in cancer patients. It has been demonstrated that neutrophils are indispensable for its anti-tumour effectiveness. We decided to evaluate the extent of the anti-tumour effectiveness of PDT combined with administration of granulocyte colony-stimulating factor (G-CSF) as well as the influence of Photofrin®and G-CSF on the myelopoiesis and functional activity of neutrophils in mice. An intensive treatment with G-CSF significantly potentiated anti-tumour effectiveness of Photofrin®-based PDT resulting in a reduction of tumour growth and prolongation of the survival time of mice bearing two different tumours: colon-26 and Lewis lung carcinoma. Moreover, 33% of C-26-bearing mice were completely cured of their tumours after combined therapy and developed a specific and long-lasting immunity. The tumours treated with both agents contained more infiltrating neutrophils and apoptotic cells then tumours treated with either G-CSF or PDT only. Importantly, simultaneous administration of Photofrin®and G-CSF stimulated bone marrow and spleen myelopoiesis that resulted in an increased number of neutrophils demonstrating functional characteristics of activation. Potentiated anti-tumour effects of Photofrin®-based PDT combined with G-CSF observed in two murine tumour models suggest that clinical trials using this tumour therapy protocol would be worth pursuing. © 2000 Cancer Research Campaign

Keywords: photodynamic therapy, Photofrin®, G-CSF, neutrophils

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Selected References

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  1. Ahmad N., Feyes D. K., Agarwal R., Mukhtar H. Photodynamic therapy results in induction of WAF1/CIP1/P21 leading to cell cycle arrest and apoptosis. Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6977–6982. doi: 10.1073/pnas.95.12.6977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Albert M. L., Pearce S. F., Francisco L. M., Sauter B., Roy P., Silverstein R. L., Bhardwaj N. Immature dendritic cells phagocytose apoptotic cells via alphavbeta5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. J Exp Med. 1998 Oct 5;188(7):1359–1368. doi: 10.1084/jem.188.7.1359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ben-Hur E., Heldman E., Crane S. W., Rosenthal I. Release of clotting factors from photosensitized endothelial cells: a possible trigger for blood vessel occlusion by photodynamic therapy. FEBS Lett. 1988 Aug 15;236(1):105–108. doi: 10.1016/0014-5793(88)80294-1. [DOI] [PubMed] [Google Scholar]
  4. Dougherty T. J., Gomer C. J., Henderson B. W., Jori G., Kessel D., Korbelik M., Moan J., Peng Q. Photodynamic therapy. J Natl Cancer Inst. 1998 Jun 17;90(12):889–905. doi: 10.1093/jnci/90.12.889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fady C., Reisser D., Martin F. Non-activated rat neutrophils kill syngeneic colon tumor cells by the release of a low molecular weight factor. Immunobiology. 1990 Aug;181(1):1–12. doi: 10.1016/S0171-2985(11)80160-9. [DOI] [PubMed] [Google Scholar]
  6. Fingar V. H., Wieman T. J., Wiehle S. A., Cerrito P. B. The role of microvascular damage in photodynamic therapy: the effect of treatment on vessel constriction, permeability, and leukocyte adhesion. Cancer Res. 1992 Sep 15;52(18):4914–4921. [PubMed] [Google Scholar]
  7. Foster T. H., Primavera M. C., Marder V. J., Hilf R., Sporn L. A. Photosensitized release of von Willebrand factor from cultured human endothelial cells. Cancer Res. 1991 Jun 15;51(12):3261–3266. [PubMed] [Google Scholar]
  8. Gołab J., Stokłosa T., Zagozdzon R., Kaca A., Giermasz A., Pojda Z., Machaj E., Dabrowska A., Feleszko W., Lasek W. G-CSF prevents the suppression of bone marrow hematopoiesis induced by IL-12 and augments its antitumor activity in a melanoma model in mice. Ann Oncol. 1998 Jan;9(1):63–69. doi: 10.1023/a:1008266321552. [DOI] [PubMed] [Google Scholar]
  9. Gołab J., Stokłosa T., Zagozdzon R., Kaca A., Kulchitska L. A., Feleszko W., Kawiak J., Hoser G., Głowacka E., Dabrowska A. Granulocyte-macrophage colony-stimulating factor potentiates antitumor activity of interleukin-12 in melanoma model in mice. Tumour Biol. 1998;19(2):77–87. doi: 10.1159/000029978. [DOI] [PubMed] [Google Scholar]
  10. Granville D. J., Levy J. G., Hunt D. W. Photodynamic therapy induces caspase-3 activation in HL-60 cells. Cell Death Differ. 1997 Oct;4(7):623–628. doi: 10.1038/sj.cdd.4400286. [DOI] [PubMed] [Google Scholar]
  11. Hunt D. W., Jiang H., Levy J. G. Photofrin increases murine spleen cell transferrin receptor expression and responsiveness to recombinant myeloid and erythroid growth factors. Immunopharmacology. 1998 Jan;38(3):267–278. doi: 10.1016/s0162-3109(97)00086-6. [DOI] [PubMed] [Google Scholar]
  12. Hunt D. W., Sorrenti R. A., Renke M. E., Waterfield E., Levy J. G. Accelerated myelopoietic recovery in irradiated mice treated with Photofrin. Int J Immunopharmacol. 1995 Jan;17(1):33–39. doi: 10.1016/0192-0561(94)00078-3. [DOI] [PubMed] [Google Scholar]
  13. Kashtan H., Haddad R., Yossiphov Y., Bar-On S., Skornick Y. Photodynamic therapy of colorectal cancer using a new light source: from in vitro studies to a patient treatment. Dis Colon Rectum. 1996 Apr;39(4):379–383. doi: 10.1007/BF02054050. [DOI] [PubMed] [Google Scholar]
  14. Korbelik M., Dougherty G. J. Photodynamic therapy-mediated immune response against subcutaneous mouse tumors. Cancer Res. 1999 Apr 15;59(8):1941–1946. [PubMed] [Google Scholar]
  15. Korbelik M. Induction of tumor immunity by photodynamic therapy. J Clin Laser Med Surg. 1996 Oct;14(5):329–334. doi: 10.1089/clm.1996.14.329. [DOI] [PubMed] [Google Scholar]
  16. Korbelik M., Krosl G., Krosl J., Dougherty G. J. The role of host lymphoid populations in the response of mouse EMT6 tumor to photodynamic therapy. Cancer Res. 1996 Dec 15;56(24):5647–5652. [PubMed] [Google Scholar]
  17. Korbelik M., Naraparaju V. R., Yamamoto N. Macrophage-directed immunotherapy as adjuvant to photodynamic therapy of cancer. Br J Cancer. 1997;75(2):202–207. doi: 10.1038/bjc.1997.34. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Krosl G., Korbelik M., Dougherty G. J. Induction of immune cell infiltration into murine SCCVII tumour by photofrin-based photodynamic therapy. Br J Cancer. 1995 Mar;71(3):549–555. doi: 10.1038/bjc.1995.108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Krosl G., Korbelik M., Krosl J., Dougherty G. J. Potentiation of photodynamic therapy-elicited antitumor response by localized treatment with granulocyte-macrophage colony-stimulating factor. Cancer Res. 1996 Jul 15;56(14):3281–3286. [PubMed] [Google Scholar]
  20. Nseyo U. O., Whalen R. K., Duncan M. R., Berman B., Lundahl S. L. Urinary cytokines following photodynamic therapy for bladder cancer. A preliminary report. Urology. 1990 Aug;36(2):167–171. doi: 10.1016/0090-4295(90)80220-h. [DOI] [PubMed] [Google Scholar]
  21. Ochsner M. Photophysical and photobiological processes in the photodynamic therapy of tumours. J Photochem Photobiol B. 1997 May;39(1):1–18. doi: 10.1016/s1011-1344(96)07428-3. [DOI] [PubMed] [Google Scholar]
  22. Pass H. I. Photodynamic therapy in oncology: mechanisms and clinical use. J Natl Cancer Inst. 1993 Mar 17;85(6):443–456. doi: 10.1093/jnci/85.6.443. [DOI] [PubMed] [Google Scholar]
  23. Reynolds T. Photodynamic therapy expands its horizons. J Natl Cancer Inst. 1997 Jan 15;89(2):112–114. doi: 10.1093/jnci/89.2.112. [DOI] [PubMed] [Google Scholar]
  24. Stoppacciaro A., Melani C., Parenza M., Mastracchio A., Bassi C., Baroni C., Parmiani G., Colombo M. P. Regression of an established tumor genetically modified to release granulocyte colony-stimulating factor requires granulocyte-T cell cooperation and T cell-produced interferon gamma. J Exp Med. 1993 Jul 1;178(1):151–161. doi: 10.1084/jem.178.1.151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Welte K., Gabrilove J., Bronchud M. H., Platzer E., Morstyn G. Filgrastim (r-metHuG-CSF): the first 10 years. Blood. 1996 Sep 15;88(6):1907–1929. [PubMed] [Google Scholar]
  26. Zilocchi C., Stoppacciaro A., Chiodoni C., Parenza M., Terrazzini N., Colombo M. P. Interferon gamma-independent rejection of interleukin 12-transduced carcinoma cells requires CD4+ T cells and Granulocyte/Macrophage colony-stimulating factor. J Exp Med. 1998 Jul 6;188(1):133–143. doi: 10.1084/jem.188.1.133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. de Vree W. J., Essers M. C., de Bruijn H. S., Star W. M., Koster J. F., Sluiter W. Evidence for an important role of neutrophils in the efficacy of photodynamic therapy in vivo. Cancer Res. 1996 Jul 1;56(13):2908–2911. [PubMed] [Google Scholar]

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