Abstract
Immunophototherapy of cancer combines the specificity of a monoclonal antibody (MAb) to an overexpressed tumor marker with the phototoxic properties of the conjugated dye. To analyze the potential role of internalisation of the dye on photo-induced cytotoxicity, we compared two target antigens, carcinoembryonic antigen (CEA) that does not internalise and ErbB2 that does. Human ovarian carcinoma SKOv3 cells that express a high level of ErbB2 were transfected with the CEA cDNA. Using FACS analysis, the resulting cell line, SKOv3-CEA-1B9, demonstrated comparable levels of expression of the two target antigens. Aluminium tetrasulfophthalocyanine (AlPcS4) was covalently coupled to anti-CEA MAb 35A7, anti-ErbB2 MAb FSP77 and a non-specific MAb PX, via a five-carbon sulfonamide spacer chain (A1) at molar ratios ranging from 6 to 9 moles of AlPcS4 per mole of MAb. The 35A7-(AlPcS4A1)8 conjugate induced 68% growth inhibition of the SKOv3-CEA-1B9 cell line after a 20h incubation at 2.50μg/ml (based on AlPcS4A1 content) following light exposure. However, the FSP77-(AlPcS4A1)6 conjugate gave a 51% growth inhibition for an AlPcS4A1 concentration as low as 0.04μg/ml after the same incubation time and exposure to the same light dose. At a 1.25μg/ml AlPcS4A1 concentration, the FSP77-(AlPcS4A1)6 conjugate gave a 67% growth inhibition after an incubation time as short as 1h, reaching a 96% inhibition after an 8h incubation time. Using an unique cell line that expresses two different target antigens, we demonstrated a clear advantage of an internalising over a non-internalising MAb-dye conjugate in terms of phototoxic efficacy. in vivo evaluation of the photodynamic properties of the conjugates is in progress. © 2001 Cancer Research Campaign http://www.bjcancer.com
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Abbreviations
- MAb:
-
monoclonal antibody
- PBS:
-
phosphate-buffered saline
- EDC:
-
1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride
- sulfo-NHS:
-
N-hydroxysulfosuccinimide
- AlPcS4:
-
aluminium tetrasulfophthalocyanine
- CEA:
-
carcinoembryonic antigen
- Al:
-
five carbon spacer chain
- Px:
-
IgG1 purified from mouse myeloma P3-X63
- %ID/g:
-
percentage of injected dose per gram
- PS:
-
photosensitizer
- IPT:
-
immunophototherapy
- mTHPC:
-
metatetrahydroxyphenylchlorin
References
Brasseur N, Langlois R, La Madeleine C, Ouellet R and van Lier JE (1999) Receptor-mediated targeting of phthalocyanines to macrophages via covalent coupling to native or maleylated bovine serum albumin. Photochem Photobiol 69: 345–352
Carcenac M, Larroque C, Langlois R, Van Lier JE, Artus JC and Pèlegrin A (1999) Preparation, phototoxicity and biodistribution studies of anti-CEA MAb-phthalocyanine conjugates. Photochem Photobiol 70: 930–936
Del Governatore M, Hamblin MR, Shea CR, Rizvi I, Molpus KG, Tanabe KK and Hasan T (2000a) Experimental photoimmunotherapy of hepatic metastases of colorectal cancer with a 17.1A chlorin e6 immunoconjugate. Cancer Res 60: 4200–4205
Del Governatore M, Hamblin MR, Piccinini EE, Ugolini G and Hasan T (2000b) Targeted photodestruction of human colon cancer cells using charged 17.1A chlorin e6 immunoconjugates. Br J Cancer 82: 56–64
Dougherty TJ, Gomer CJ, Henderson BW, Jori G, Kessel D, Korbelik M, Moan J and Peng Q (1998) Photodynamic therapy. J Natl Cancer Inst 90: 889–905
Duska LR, Hamblin MR, Bamberg MP and Hasan T (1997) Biodistribution of charged F(ab’)2 photoimmunoconjugates in a xenograft model of ovarian cancer. Br J Cancer 75: 837–844
Goff BA, Hermanto U, Rumbaugh J, Blake J, Bamberg M and Hasan T (1994) Photoimmunotherapy and biodistribution with an OC125-chlorin immunoconjugate in an in vivo murine ovarian cancer model. Br J Cancer 70: 474–480
Gutowski M, Carcenac M, Pourquier D, Larroque C, Rouanet P and Pèlegrin A (2001) Intraoperative immunophotodetection for radical resection of cancer: evaluation in an experimental model. Clin Cancer Res, In Press
Hamblin MR, Del Governatore M, Rizvi I and Hasan T (2000) Biodistribution of charged 17.1A photoimmunoconjugates in a murine model of hepatic metastasis of colorectal cancer. Br J Cancer 83: 1544–1551
Hamblin MR, Miller JL and Hasan T (1996) Effect of charge on the interaction of site-specific photoimmunoconjugates with human ovarian cancer cells. Cancer Res 56: 5205–5210
Harwerth IM, Wels W, Marte BM and Hynes NE (1992) Monoclonal antibodies against the extracellular domain of the erbB-2 receptor function as partial ligand agonists. J Biol Chem 267: 15160–15167
Kohler G, Howe SC and Milstein C (1976) Fusion between immunoglobulin-secreting and nonsecreting myeloma cell lines. Eur J Immunol 6: 292–295
Merlin JL, Azzi S, Lignon D, Ramacci C, Zeghari N and Guillemin F (1992) MTT assays allow quick and reliable measurement of the response of human tumour cells to photodynamic therapy. Eur J Cancer 28A: 1452–1458
Mew D, Wat CK, Towers GHN and Levy JG (1983) Photoimmunotherapy: treatment of animal tumors with tumor-specific monoclonal antibody-hematoporphyrin conjugates. J Immunol 130: 1473–1477
Oseroff AR, Ohuoha D, Hasan T, Bommer JC and Yarmush ML (1986) Antibody-targeted photolysis: selective photodestruction of human T-cell leukemia cells using monoclonal antibody-chlorin e6 conjugates. Proc Natl Acad Sci USA 83: 8744–8748
Pèlegrin A, Folli S, Buchegger F, Mach JP, Wagnières G and van den Bergh H (1991) Antibody-fluorescein conjugates for photoimmunodiagnosis of human colon carcinoma in nude mice. Cancer 67: 2529–2537
Pèlegrin A, Terskikh A, Hayoz D, Chalandon Y, Olsson NO, Folli S, Buchegger F, Kromer B, Schwarz K, Martin M, Martin F and Mach JP (1992) Human carcinoembryonic antigen cDNA expressed in rat carcinoma cells can function as target antigen for tumor localization of antibodies in nude rats and as rejection antigen in syngeneic rats. Int J Cancer 52: 110–119
Vrouenraets MB, Visser GW, Loup C, Meunier B, Stigter M, Oppelaar H, Stewart FA, Snow GB and van Dongen GA (2000) Targeting of a hydrophilic photosensitizer by use of internalizing monoclonal antibodies: A new possibility for use in photodynamic therapy. Int J Cancer 88: 108–114
Vrouenraets MB, Visser GW, Stewart FA, Stigter M, Oppelaar H, Postmus PE, Snow GB and van Dongen GA (1999) Development of meta-tetrahydroxyphenylchlorin-monoclonal antibody conjugates for photoimmunotherapy. Cancer Res 59: 1505–1513
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Carcenac, M., Dorvillius, M., Garambois, V. et al. Internalisation enhances photo-induced cytotoxicity of monoclonal antibody-phthalocyanine conjugates. Br J Cancer 85, 1787–1793 (2001). https://doi.org/10.1054/bjoc.2001.2170
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DOI: https://doi.org/10.1054/bjoc.2001.2170
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