Abstract
Keyhole limpet hemocyanin (KLH) is widely used as a carrier molecule to enhance immune responses to administered antigens, and for immunotherapy of bladder and renal carcinoma. In the present study we show, using lectin and antibody binding studies, that native KLH contains Gal(β1–3)GalNAc-bearing oligosaccharides, and that immunization with KLH in Lewis rats induces the production of anti-Gal(β1–3)GalNAc antibodies. This might explain the beneficial effect of KLH in bladder cancers that express crossreactive Gal(β1–3)GalNAc determinants or the T antigen.
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Dubois M, Gilles KA, Hamilton JK, Rebers PA, Smith F (1956) Colorimetric method for determination of sugars and related substances. Anal Chem 28:350
Fung PYS, Madej M, Koganty RR, Longenecker BM (1990) Active specific immunotherapy of a murine mammary adenocarcinoma using a synthetic tumor-associated glycoconjugate. Cancer Res 50:4308
Grzych J-M, Dissous C, Capron M, Torres S, Lambert P-H, Capron A (1987)Schistosoma mansoni shares a protective carbohydrate epitope with keyhole limpet hemocyanin. J Exp Med 165:865
Helling F, Shang A, Calves M, Zhang S, Ren S, Yu RK, Oettgen HF, Livingston PO (1994) GD3 vaccines for melanoma: superior immunogenicity of keyhole limpet hemocyanin conjugate vaccines. Cancer Res 54:197
Henningsson CM, Selvaraj S, MacLean GD, Suresh MR, Noujaim AA, Longenecker BM (1987) T cell recognition of a tumor-associated glycoprotein and its synthetic carbohydrate epitopes: stimulation of anticancer T cell immunity in vivo. Cancer Immunol Immunother 25:231
Langkilde NC, Wolf H, Clausen H, Ørntoft TF (1992) Human urinary bladder carcinoma glycoconjugates expressing T (Galβ(1–3)GalNAcα1-O-R) and T-like antigens: a comparative study using peanut agglutinin and poly- and monoclonal antibodies. Cancer Res 52:5030
Langkilde NC, Wolf H, Clausen H, Kjeldsen T, Ørntoft TF, (1992) Nuclear volume and expression of T-antigen, sialosyl-Tn-antigen, and Tn-antigen in carcinoma of the human bladder. Cancer 69:219
Ledeen RW, Yu RK (1982) Gangliosides: structure, isolation and analysis. Methods Enzymol 83:139
Longenecker BM, MacLean GD, McEwan AJB, Sykes T, Henningsson C, Suresh MR, Noujaim AA (1988) Synthetic Thomsen Friedenreich antigens for production of anti-carcinoma monoclonal antibodies and generation of anti-carcinoma T cells. UCLA Symp Mol Cell Biol 79:307
MacLean GD, Bowen-Yacyshyn MB, Samuel J, Meikle A, Stuart G, Nation J, Poppema S, Jerry M, Koganty R, Wong T, Longenecker BM (1992) Active immunization of human ovarian cancer patients against a common carcinoma (Thomsen-Friedenreich) determinant using a synthetic carbohydrate antigen. J Immunother 11:292
MacLean GD, Reddish M, Koganty RR, Wong T, Gandhi S, Smolenski M, Samuel J, Nabholtz JM, Longenecker BM (1993) Immunization of breast cancer patients using a synthetic sialyl-Tn glycoconjugate plus Detox adjuvant. Cancer Immunol Immunother 36:215
Momoi T, Tokunaga T, Nagai Y (1982) Specific interaction of peanut agglutinin with the glycolipid asialo GM1. FEBS Lett 141:6
Sadiq SA, Thomas FP, Kilidreas K, Protopsaltis S, Hays AP, Lee KW, Romas SN, Kumar N, Berg L van den, Santoro M, Lange DJ, Younger DS, Lovelace RE, Trojaborg W, Sherman WH, Miller JR, Minuk J, Fehr MA, Roelofs RI, Hollander D, Nichols FT III, Mitsumoto H, Kelley JJ, Swift TR, Munsat TL, Latov N (1990) The spectrum of neurologic disease associated with anti-GM1 antibodies. Neurology 40:1067
Sargent ER, Williams RD (1992) Immunotherapeutic alternatives in superficial bladder cancer. Urol Clin N Am 19:581
Singhal A, Fohn M, Hakomori S-H (1991) Induction of α-N-acetylgalactosamine-O-serine/threonine (Tn) antigen-mediated cellular immune response for active immunotherapy in mice. Cancer Res 51:1406
Springer GF (1984) T and Tn, general carcinoma autoantigen. Science 224:1198
Thomas FP, Trojaborg W, Nagy C, Santoro M, Sadiq SA, Latov N, Hays AP (1991) Experimental autoimmune neuropathy with anti-GM1 antibodies and immunoglobulin deposits at the nodes of Ranvier. Acta Neuropathol 82:378
Woodward MP, Young WW Jr, Bloodgood RA (1985) Detection of monoclonal antibodies specific for carbohydrate epitopes using periodate oxidation. J Immunol Methods 78:143–153
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Supported by NIH grant NS11766 and by the William Rosenwald Family Fund Inc.
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Wirguin, I., Suturkova-Milosević, L., Briani, C. et al. Keyhole limpet hemocyanin contains Gal(β1–3)-GalNAc determinants that are cross-reactive with the T antigen. Cancer Immunol Immunother 40, 307–310 (1995). https://doi.org/10.1007/BF01519630
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DOI: https://doi.org/10.1007/BF01519630