Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1997;75(2):202–207. doi: 10.1038/bjc.1997.34

Macrophage-directed immunotherapy as adjuvant to photodynamic therapy of cancer.

M Korbelik 1, V R Naraparaju 1, N Yamamoto 1
PMCID: PMC2063270  PMID: 9010027

Abstract

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-1 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.

Full text

PDF
203

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cho Y. H., Straight R. C., Smith J. A., Jr Effects of photodynamic therapy in combination with intravesical drugs in a murine bladder tumor model. J Urol. 1992 Mar;147(3):743–746. doi: 10.1016/s0022-5347(17)37370-6. [DOI] [PubMed] [Google Scholar]
  2. Cooke N. E., Haddad J. G. Vitamin D binding protein (Gc-globulin). Endocr Rev. 1989 Aug;10(3):294–307. doi: 10.1210/edrv-10-3-294. [DOI] [PubMed] [Google Scholar]
  3. Elmets C. A., Bowen K. D. Immunological suppression in mice treated with hematoporphyrin derivative photoradiation. Cancer Res. 1986 Apr;46(4 Pt 1):1608–1611. [PubMed] [Google Scholar]
  4. Evans S., Matthews W., Perry R., Fraker D., Norton J., Pass H. I. Effect of photodynamic therapy on tumor necrosis factor production by murine macrophages. J Natl Cancer Inst. 1990 Jan 3;82(1):34–39. doi: 10.1093/jnci/82.1.34. [DOI] [PubMed] [Google Scholar]
  5. Fisher A. M., Murphree A. L., Gomer C. J. Clinical and preclinical photodynamic therapy. Lasers Surg Med. 1995;17(1):2–31. doi: 10.1002/lsm.1900170103. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Korbelik M., Krosl G. Enhanced macrophage cytotoxicity against tumor cells treated with photodynamic therapy. Photochem Photobiol. 1994 Nov;60(5):497–502. doi: 10.1111/j.1751-1097.1994.tb05140.x. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. Krosl G., Korbelik M. Potentiation of photodynamic therapy by immunotherapy: the effect of schizophyllan (SPG). Cancer Lett. 1994 Aug 29;84(1):43–49. doi: 10.1016/0304-3835(94)90356-5. [DOI] [PubMed] [Google Scholar]
  11. Link R. P., Perlman K. L., Pierce E. A., Schnoes H. K., DeLuca H. F. Purification of human serum vitamin D-binding protein by 25-hydroxyvitamin D3-Sepharose chromatography. Anal Biochem. 1986 Sep;157(2):262–269. doi: 10.1016/0003-2697(86)90624-x. [DOI] [PubMed] [Google Scholar]
  12. Lynch D. H., Haddad S., King V. J., Ott M. J., Straight R. C., Jolles C. J. Systemic immunosuppression induced by photodynamic therapy (PDT) is adoptively transferred by macrophages. Photochem Photobiol. 1989 Apr;49(4):453–458. doi: 10.1111/j.1751-1097.1989.tb09194.x. [DOI] [PubMed] [Google Scholar]
  13. Myers R. C., Lau B. H., Kunihira D. Y., Torrey R. R., Woolley J. L., Tosk J. Modulation of hematoporphyrin derivative-sensitized phototherapy with corynebacterium parvum in murine transitional cell carcinoma. Urology. 1989 Mar;33(3):230–235. doi: 10.1016/0090-4295(89)90399-3. [DOI] [PubMed] [Google Scholar]
  14. Naraparaju V. R., Yamamoto N. Roles of beta-galactosidase of B lymphocytes and sialidase of T lymphocytes in inflammation-primed activation of macrophages. Immunol Lett. 1994 Dec;43(3):143–148. doi: 10.1016/0165-2478(94)90214-3. [DOI] [PubMed] [Google Scholar]
  15. Suit H. D., Sedlacek R. S., Silver G., Dosoretz D. Pentobarbital anesthesia and the response of tumor and normal tissue in the C3Hf/sed mouse to radiation. Radiat Res. 1985 Oct;104(1):47–65. [PubMed] [Google Scholar]
  16. Yamamoto N., Homma S. Vitamin D3 binding protein (group-specific component) is a precursor for the macrophage-activating signal factor from lysophosphatidylcholine-treated lymphocytes. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8539–8543. doi: 10.1073/pnas.88.19.8539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Yamamoto N., Hoober J. K., Yamamoto N., Yamamoto S. Tumoricidal capacities of macrophages photodynamically activated with hematoporphyrin derivative. Photochem Photobiol. 1992 Aug;56(2):245–250. doi: 10.1111/j.1751-1097.1992.tb02153.x. [DOI] [PubMed] [Google Scholar]
  18. Yamamoto N., Lindsay D. D., Naraparaju V. R., Ireland R. A., Popoff S. N. A defect in the inflammation-primed macrophage-activation cascade in osteopetrotic rats. J Immunol. 1994 May 15;152(10):5100–5107. [PubMed] [Google Scholar]
  19. Yamamoto N., Naraparaju V. R. Role of vitamin D3-binding protein in activation of mouse macrophages. J Immunol. 1996 Aug 15;157(4):1744–1749. [PubMed] [Google Scholar]
  20. Yamamoto N., St Claire D. A., Jr, Homma S., Ngwenya B. Z. Activation of mouse macrophages by alkylglycerols, inflammation products of cancerous tissues. Cancer Res. 1988 Nov 1;48(21):6044–6049. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES