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Neuraminidase and tumor immunotherapy

Neuraminidase und Tumor-Immuntherapie

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Zusammenfassung

Erste Ergebnisse aus klinischen Versuchen mit dem Enzym Neuraminidase machen auf eine neue Art der wirksamen Tumorbehandlung aufmerksam. Eingang in die Klinik fand diese vielversprechende Tumor-Immuntherapie nach erfolgreichen tierexperimentellen Studien an tumortragenden Mäusen, Ratten und Hunden. In einer Übersicht sind die derzeit bekannten und wesentlichen experimentellen und klinischen Ergebnisse über die Tumor-Immuntherapie mit Neuraminidase und die in diesem Zusammenhang notwendigen kritischen Überlegungen dargestellt. Darüberhinaus wird versucht, aus der breiten Vielfalt der biochemischen und biologischen Ergebnisse aus in-vitro Studien die wichtigeren Erkenntnisse auszuwählen, die zum Begreifen der noch weitgehend ungeklärten Wirkungsweise des Enzyms in-vivo beitragen können.

In einem kurzen ersten Abschnitt (1.0) sind die charakteristischen biochemischen Daten des Enzyms Neuraminidase aufgeführt. Der zweite Teil (2.0) enthält etwas ausführlicher die Erkenntnisse über die Wirkung der Neuraminidase auf das Verhalten von behandelten Zellen: Hierbei werden einerseits die biophysikalischen und biochemischen Veränderungen angesprochen sowie die sog. „demaskierenden“ Effekte überdacht und andererseits wird die Wirkung auf die immunologisch antwortenden Zellen erörtert. In einem drittenTeil (3.0) sind die unterschiedlichen Befunde aus Tierexperimenten mit Neuraminidasebehandelten Tumorzellen gegenübergestellt, wobei zwischen Tumortransplantations-Experimenten und Tumortherapie-Versuchen unterschieden wurde. Der letzte Abschnitt (4.0) berichtet über die ersten tumortherapeutischen klinischen Studien mit Neuraminidase-behandelten autologen und homologen Tumorzellen, die zum Teil sehr überraschende und erstaunliche Erfolge erbracht haben.

Auf der Grundlage neuerer Befunde aus der Arbeitsgruppe der Autoren werden frühere, zum Teil widersprechende Ergebnisse aus verschiedenen Arbeitsgruppen kritisch überdacht. Auf die Fragen nach der Veränderung der Antigenität und anderer Zelleigenschaften durch die Abspaltung der membrangebundenen Neuraminsäure, der Adjuvanswirksamkeit von Neuraminidase selbst, der Beziehung zwischen erfolgreicher Therapie und Dosisabhängigkeit zum einen und der Beziehung zwischen unerwünschten Methoden zur Reduktion der Tumormasse und immunologischem Reaktionsvermögen des Tumorträgers zum anderen wird besonders eingegangen.

Summary

Preliminary results of first clinical studies with the enzyme neuraminidase call attention to a new kind of cancer treatment. This promising approach to tumor immunotherapy was entered into the clinical phase as a consequence of successful experimental studies in tumor-bearing mice, rats and dogs. In this review, the presently known and essential results of experimental and clinical studies on tumor immunotherapy by means of neuraminidase are presented as well as some necessary and critical considerations in this context. Moreover, out of a broad variety of results of biochemical and biological in vitro studies, it was attempted to select the more essential knowledge which could contribute to a better understanding of the still rather unclear in vivo mode of action of the enzyme neuraminidase.

In a first brief paragraph (1.0), the biochemically characteristic data of the enzyme neuraminidase is presented. In the second section (2.0), the basic knowledge about the effects of neuraminidase on cell behavior is rather amply contained. Here, on the one hand, the biophysical and biochemical alterations are mentioned, the so-called “unmasking” effects are reconsidered and, on the other hand, the effects on the immunologically responding cell are discussed. In a third section (3.0), the diverse findings from animal experiments using neuraminidase-treated tumor cells are confronted, whereby tumor transplantation experiments and tumor therapy experiments are dealt with separately. The last section (4.0) reports about the first clinical studies with neuraminidase-treated autologous as well as homologous tumor cells, which partly brought about rather surprising and astonishing success.

On the basis of recent findings by the study group of the authors, the more prior and sometimes discrepant results of various groups are critically considered. The problems of alteration of antigenicity and of other properties of cells through splitting off membrane-bound neuraminic acid, the facts of adjuvanticity of neuraminidase itself, the relation of successful therapy to dose dependency as well as the relation of undesirable methods for tumor mass reduction to the immunological responsiveness of the tumor bearer were especially looked into.

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References

  1. Ada, G.L., Stone, J.D.: Electrophoretic studies of virus red cell interaction: Mobility gradient of cells treated with viruses of the influenza group and the receptor destroying enzyme of V. cholerae. Br. J. Exp. Path.31, 263 (1950)

    Google Scholar 

  2. Ada, G.L., French, E.L.: Purification of bacterial neuraminidase (receptor-destroying enzyme). Nature183, 1740 (1959)

    Google Scholar 

  3. Albright, L., Madigan, J.C., Gaston, M.R., Houchens, D.P.: Therapy in an intracerebral murine glioma model, usingBacillus Calmette-Guérin, neuraminidase-treated tumor cells, and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. Cancer Research35, 658 (1975)

    Google Scholar 

  4. Ambrose, E.J., James, A.M., Lowice, J.H.: Differences between the electrical charge carried by normal and homologous tumor cells. Nature (Lond.)177, 576 (1956)

    Google Scholar 

  5. Bagshawe, K.D., Currie, G.A.: Immunogenicity of L1210 murine leukemia cells after treatment with neuraminidase. Nature (Lond.)218, 1254 (1968)

    Google Scholar 

  6. Barth, R.F., Singla, O.: Alterations in the immunogenicity and antigenicity of mammalian erythrocytes following treatment with neuraminidase (3770). Proc. of the Soc. for Exp. Biology and Medicine145, 168 (1974)

    Google Scholar 

  7. Bekesi, J.G., St. Arneault, G., Holland J.F.: Increase of leukemia L1210 immunogenicity byVibrio cholerae neuraminidase treatment. Cancer Res.31, 2130 (1971)

    Google Scholar 

  8. Bekesi, J.G., St. Arneault, G., Walter, L., Holland, J.F.: Immunogenicity of leukemia L1210 cells after neuraminidase treatment. J. Nat. Canc. Inst.49, 107 (1972)

    Google Scholar 

  9. Bekesi, J.G., Roboz, J.P., Walter, L., Holland, J.F.: Stimulation of specific immunity against cancer by neuraminidase-treated tumor cells. Behring Inst. Mitt., No.55, 309 (1974)

    Google Scholar 

  10. Bekesi, J.G., Holland, J.F.: Chemoimmunotherapy of leukemia in man and experimental animals. Int. Conf. on Immunotherapy of Cancer, Nov. 5–7, New York (1975)

  11. Bekesi, J.G., Holland, J.F., Fleminger, R., Yates, J., Henderson, E.S.: Immunotherapeutic efficacy of neuraminidase-treated allogeneic myeloblasts in patients with acute myelocytic leukemia. J. Nat. Canc. Inst., in press (1976)

  12. Bekesi, J.G.: Immunotherapeutic efficacy of neuraminidase-treated allogeneic myeloblasts in patients with acute myeolocytic leukemia. Invited speaker, Med. Klinik, Univ. of Marburg, May 19, 1976

  13. Blix, F.G., Gottschalk, A., Klenk, E.: Proposed nomenclature in the field of neuraminidase and sialic acids. Nature179, 1088 (1957)

    Google Scholar 

  14. Boschmann, T.A.C., Jacobs, J.: The influence of ethylenediaminetetraacetate on various neuraminidase. Biochem. Z.342, 532 (1965)

    Google Scholar 

  15. Burnet, M.F.: Cancer — A biological approach. IV. Practical applications. Br. Med. J.1, 844 (1957)

    Google Scholar 

  16. Burnet, F.M.: Implications of cancer immunity. Aust. N.Z. J. Med.1, 71 (1973)

    Google Scholar 

  17. Codington, J.F., Sanford, B.H., Jeanloz, R.W.: Glycoprotein coat of the TA3 cell. I. Removal of carbohydrate and protein material from viable cells. J. Natl. Cancer Inst.45, 637 (1970)

    Google Scholar 

  18. Cook, G.M., Heard, D.H., Seaman, G.V.: Sialic acids and the electrokinetic charge of the human erythrocyte. Nature191, 44 (1961)

    Google Scholar 

  19. Cook, G.M., Jacobson, W.: The electrophoretic mobility of normal and leukaemic cells of mice. Biochem. J.107, 549 (1968)

    Google Scholar 

  20. Cormak, D.: Effect of enzymatic removal of cell surface sialic acid on the adherence of Walker 256 tumor cells to mesothelial membrane. Cancer Research30, 1459 (1970)

    Google Scholar 

  21. Currie, G.A.: Masking of antigens on the Landschütz ascites tumor. LancetII, 1336 (1967)

    Google Scholar 

  22. Currie, G.A., Bagshawe, K.D.: The effect of neuraminidase on the immunogenicity of the Landschütz ascites tumor. Site and mode of action. Br. J. Cancer22, 588 (1968)

    Google Scholar 

  23. Currie, G.A., Bagshawe, K.D.: The role of sialic acid in antigenic expression: Further studies of the Landschütz ascites tumor. Br. J. Cancer22, 843 (1968)

    Google Scholar 

  24. Currie, G.A., Bagshawe, K.D.: Tumor specific immunogenecity of methylcholanthrene-induced sarcoma cells after incubation in neuraminidase. Br. J. Cancer23, 141 (1969)

    Google Scholar 

  25. Dalmasso, A.P., Müller-Eberhard, H.J.: Interaction of autologous complement with red cells in the absence of antibody. Proc. Soc. Exp. Biol. Med.117, 643 (1964)

    Google Scholar 

  26. Defendi, V., Gasic, G.: Surface mucopolysaccharides of polyoma virus transformed cells. J. Cell. Comp. Physiol.62, 23 (1963)

    Google Scholar 

  27. Deman, J.J., Bruyneel, E.A., Mareel, M.M.: A study on the mechanism of intercellular adhesion. Effects of neuraminidase, calcium and trypsin on the aggregation of suspended HeLa cells. J. Cell Biology60, 641 (1974)

    Google Scholar 

  28. Doré, J.F., Hadjiyannakis, M.J., Guibout, C., Coudert, A., Marholev, L., Imai, K.: Use of enzyme-treated cell in immunotherapy of a murine leukemia. Lancet17, 600 (1973)

    Google Scholar 

  29. Drzeniek, R.: Differences in splitting capacity of virus and Vibrio cholerae neuraminidases on sialic acid type substrates. Biochem. Biophys. Res. Commun.26, 631 (1967)

    Google Scholar 

  30. Drzeniek, R., Gaube, A.: Differences in substrate specificity of myxovirus neuraminidases. Biochem. Biophys. Res. Commun.38, 651 (1970)

    Google Scholar 

  31. Drzeniek, R.: Viral and bacterial neuraminidases. Topics Microbiol. Immunol.59, 35, Springer-Verlag Heidelberg (1972)

    Google Scholar 

  32. Editorial: Enzyme causes cancer cells to show their colors. JAMA234, 371 (1975)

  33. Eisenberg, S., Ben-Or, S., Dolanski, F.: Elektrokinetic properties of cells in growth processes. I. The elektrokinetic behavior of liver cells during regeneration and postnatal growth. Exp. Cell Res.26, 451 (1962)

    Google Scholar 

  34. Etheredge, E.E., Shons, A.R., Najarian, J.S.: Neuraminidase-induced autologous stimulation of human leukocyte cultures. Proc. of the 6th Leukocyte Culture Conference (Ed. by M.R. Schwarz), 121, Academic Press New York (1972)

    Google Scholar 

  35. Faraci, R.P., Marrone, J.A.C., Ketchan, A.S.: Antitumor immune response following injection of neuraminidase-treated sarcoma cells. Ann. Surg.181, 359 (1975)

    Google Scholar 

  36. Fidler, I.J., Kahn, J.M., Montgomery, P.C.: Effect of neuraminidase on the rat one-way mixed lymphocyte interaction. Immunol. Commun.2(6, 573 (1973)

    Google Scholar 

  37. Flye, M.W., Reisner, E.G., Amos, D.B.: The in vitro effect of neuraminidase on human lymphocytes. J. Surg. Res.15 (1973)

  38. Friedenreich, V.: Untersuchungen über das von O. Thomsen beschriebene vermehrungsfähige Agens als Veränderer des isoagglutinatorischen Verhaltens der roten Blutkörperchen. Zeitschr. Immun. Forsch.55, 84 (1928)

    Google Scholar 

  39. Friedenreich, V.: Die serologische Auffassung des Thomsenschen Blutkörperchenreceptors. Acta path. microbiol. scand. Suppl. V, 68 (1930)

  40. Froese, G., Berczi, I., Sehon, A.H.: Brief communication: Neuraminidase-induced enhancement of tumor growth in mice. J. Nat. Cancer Inst.52, No. 6, 1905 (1974)

    Google Scholar 

  41. Fuhrmann, G.F. von, Granzer, E., Kübler, W., Rueff, F., Ruhenstroth-Bauer, G.: Neuroaminsäurenbedingte Strukturunterschiede der Zellmembranen normaler und maligner Leberzellen. Z. Naturforschg.17b, 610 (1962)

    Google Scholar 

  42. Fuhrmann, G.F.: Cytopherograms of normal proliferating and malignant rat liver cells. In: Cell Electrophoresis (Ambrose, E.J. ed.), London, Churchill, 92 (1965)

    Google Scholar 

  43. Gielen, W.: Neuraminidase in higher organisms. Behring Inst. Mitt., No.55, 85 (1974)

  44. Gottschalk, A.: Neuraminidase: The specific enzyme of influenza virus and Vibrio cholerae. Biochim. Biophys. Acta23, 645 (1957)

    Google Scholar 

  45. Gottschalk, A.: Neuraminidase: Its substrate and mode of action. Adv. Enzymol. Interscience20, 135 (1958)

    Google Scholar 

  46. Gottschalk, A., Bhargava, A.S.: Neuraminidase. In: The Enzymes, Vol. V, 3rd Ed. pp. 321, (Boyer, D. Ed.), Academic Press New York (1971)

    Google Scholar 

  47. Grimes, W.J.: Sialic acid transferases and sialic acid levels in normal and transformed cells. Biochem. J.9, 5083 (1970)

    Google Scholar 

  48. Grothaus, E.A., Flye, M.W., Yunis, E., Amos, B.D.: Human lymphocyte antigen reactivity modified by neuraminidase. Science173, 54 (1971)

    Google Scholar 

  49. Hakomori, S., Murakami, W.T.: Glycolipids of hamster fibroblasts and derived malignant-transformed cell lines. Proc. Natl. Acad. Sci. USA59, 254 (1968)

    Google Scholar 

  50. Hakomori, S.: In: 22nd Colloquium der Gesellschaft für Biologische Chemie, Ed. by D.F.H. Wallach and H. Fischer, pp. 65, Springer-Verlag New York, Heidelberg, Berlin (1971)

    Google Scholar 

  51. Han, T.: Enhancement of mixed lymphocyte reactivity by neuraminidase. Transplantation14, 515 (1972)

    Google Scholar 

  52. Han, T., Enhancement of mixed lymphocyte reactivity by neuraminidase. Transplantation14, 515 (1972)

    Google Scholar 

  53. Han, T.: Enhancement of in vitro lymphocyte reponse by neuraminidase. Clin. exp. Immunol.13, 165 (1973)

    Google Scholar 

  54. Han, T.: Enhancement of delayed skin hypersensitivity by neuraminidase in cancer patients. Clin. exp. Immunol.18, 95 (1974)

    Google Scholar 

  55. Han, T.: Specific effect of neuraminidase on blastogenic response of sensitized lymphocytes. Immunology28, 283 (1975)

    Google Scholar 

  56. Hauschka, T.S., Weiss, L., Holdridge,.: Karyotypic and surface features of murine TA3 carcinoma cells during immunoselection in mice and rats. J. Natl. Cancer, Inst.47, 343 (1971)

    Google Scholar 

  57. Holland, J.R.: Ex Pluribus Unum: Presidential Address to American Association for Cancer Research. Cancer Res.31, 1319 (1971)

    Google Scholar 

  58. Holland, J.R., St. Arneault, G., Bekesi, G.: Combined chemo-and immunotherapy of transplantable and spontancous murine leukemia. Porc. Amer. Ass. Cancer. Res.13, 83 (1972)

    Google Scholar 

  59. Holland, J.F., Bekesi, J.G.: Immunotherapy of human leukemia with neuraminidase-modified cells. Med. Clinics of North America60, 539 (1976)

    Google Scholar 

  60. Hughes, R.C., Sanford, B.H., Jeanloz, R.W.: Regeneration of the surface glycoproteins of a transplantable mouse tumor cell after treatment with neuraminidase. Proc. Natl. Acad. Sci.69, 942 (1972)

    Google Scholar 

  61. Hughes, R.C., Palmer, P.D., Sanford, B.H.: Factors involved in the cytotoxicity of normal guinea pig serum for cells of murine tumor TA3 sublines treated with neuraminidase. J. Immunol. III, No. 4, 107 (1973)

  62. Im, H.M., Simmons, R.L.: Modification of graft-versus-host disease by neuraminidase treatment of donor cells. Transplantation12, 6, 472 (1971)

    Google Scholar 

  63. Jamieson, C.W.: Enhancement of antigenicity of syngeneic murine melanoma by neuraminidase. Int. Cancer Congress Florence 1974

  64. Johannsen, R., Sedlacek, H.H.: Specificity of cytotoxic antibodies to autologous human lymphocytes treated with neuraminidase from Vibrio cholerae. Behring Inst. Mitt., No.55, 209 (1974)

    Google Scholar 

  65. Johannsen, R., Carlsson, A.B., Sedlacek, H.H.: In vitro transformation of human lymphocytes by neuraminidase from Vibrio cholerae (VCN). 6th Workshop on Leucocyte Cultures Basel, March 17–19, 1975

  66. Johannsen, R., Knop, J., Sedlacek, H.H., Seiler, F.R.: Augmentation of in vitro lymphocyte response by neuraminidase. Z. Immun.-Forsch.152, 90 (1976)

    Google Scholar 

  67. Kassulke, J.T., Stutman, O., Yunis, E.J.: Blood-group isoantigens in leukemic cells. Reversibility of Isoantigenic changes by neuraminidase. J. Natl. Cancer Inst.46, 1201 (1971)

    Google Scholar 

  68. Kemp, R.B.: Effect of the removal of cell surface sialic acids on cell aggregation in vitro. Nature (Lond.)218, 1255 (1968)

    Google Scholar 

  69. Keenan, T.W., Morré, D.J.: Mammary carcinoma: Enzymatic block indisialoganglioside biosynthesis. Science182, 935 (1973)

    Google Scholar 

  70. Kim, Z., Uhlenbruck, G.: Untersuchungen über T-Antigen und T-Agglutinin. Z. Immun. Forsch.130, 88 (1966)

    Google Scholar 

  71. Knop, J.: Enhancement of phagocytosis by Vibrio cholerae neuraminidase (VCN). 3rd Europ. Immunol. Meeting, Copenhagen, Aug. 25–27, 1976

  72. Knop, J., Sedlacek, H.H., Seiler, F.R.: Stimulation of the antibody to various antigens by Vibrio cholerae neuraminidase (VCN). Z. Immun.-Forsch.152, 94 (1976)

    Google Scholar 

  73. Kollmorgen, G.M., Erwin, D.N., Killion, J.J., Hoge, A.F., Sansing, W.A.: Combination chemotherapy and immunotherapy of transplantable murine leukemia. Proc. Amer. Ass. Cancer Res.14, 69 (1973)

    Google Scholar 

  74. Kuhn, R., Brossmer, R.: Über O-Acetyl-lactaminsäurelactose aus Kuhcolostrum und ihre Spaltbarkeit durch Influenzavirus. Ber. detsch. chem. Ges.89, 2013 (1956)

    Google Scholar 

  75. Lagrange, P.H., Mackaness, G.B., Miller, T.E.: Influence of dose and route of antigen injection on the immunological induction of T cells. J. exp. Med.139, 528 (1974)

    Google Scholar 

  76. Lee, A.: Effect of neuraminidase on the phagocytosis of heterologous red cells by mouse peripheral macrophages. Proc. Soc. Exp. Biol. Med.128, 891 (1968)

    Google Scholar 

  77. Lindahl-Kiessling, K., Peterson, R.D.A.: The mechanism of phytohemagglutinin action. III. Stimulation of lymphocytes by allogeneic lymphocytes and phytohemagglutinin. Exp. Cell. Res.55, 85 (1969)

    Google Scholar 

  78. Lindenman, J., Klein, P.A.: Immunological aspects of viral oncolysis. Recent advances in cancer research, Vol.9, 66, Springer-Verlag Berlin (1967)

    Google Scholar 

  79. Lüben, G., Sedlacek, H.H., Seiler, F.R.: Binding of Vibrio cholerae neuraminidase (VCN) to peripheral blood lymphocytes and to cultured lymphoblastoid cells. Behring Inst. Mitt., No.59, 30 (1976)

    Google Scholar 

  80. Lundgreen, G., Jeitz, L., Lundin, L., Simmons, R.L.: Increased stimulation by neuraminidase-treated cells in mixed lymphocyte cultures. Fed. Proc.30, 395 (1971)

    Google Scholar 

  81. Lundgren, G., Simmons, R.L.: Effect of neuraminidase on the stimulatory capacity of cells in human mixed lymphocyte cultures. Clin. and Exp. Immunol.9, 6, 915 (1971)

    Google Scholar 

  82. Mathé, G., Halle-Pannenka, O., Bourut, C.: Active immunotherapy of AKR mice spontaneous leukemia. Rev. Europ. Etudes Clin. et Biol.XVII, 997 (1973)

    Google Scholar 

  83. Mayhew, E.: Cellular electrophoretic mobility and the mitotic cycle. J. gen. Physiol.49, 717 (1966)

    Google Scholar 

  84. Mayhew, E., Weiss, L.: Ribonucleic acid at the periphery of different cell types and effect of growth rate on ionogenic groups in the periphery of cultured cells. Exp. Cell Res.50, 441 (1968)

    Google Scholar 

  85. McQuiddy, P., Lilien, J.E.: The binding of exogenously added neuraminidase to cells and tissues in culture. Biochim et Biophys. Acta291, 774 (1973)

    Google Scholar 

  86. Mehrishi, J.N., Zeiller, K., Sachtleben, P.: Murine T and B lymphocytes: The effect of neuraminidase and anti-neuraminidase serum on the surface charge of enzyme-treated cells. Behring Inst. Mitt., No.55, 243 (1974)

    Google Scholar 

  87. Meindl, P., Tuppy, H.: Über die Spaltung synthetischer Sialinsäure-α-Ketoside durch Neuraminidase. Mh. Chem.97, 990 (1966)

    Google Scholar 

  88. Metzgar, R.S., Mohanakumar, T., Miller, D.S.: Antigens specific for human lymphocytic and myeloid leukemia cells: Detection of nonhuman primate antiserums. Science178, 986 (1972)

    Google Scholar 

  89. Mohr, E., Schramm, G.: Reinigung und Charakterisierung der Neuraminidase aus Vibrio cholerae. Z. Naturforsch.15B, 568 (1960)

    Google Scholar 

  90. Müller, H.E.: Neuraminidases of bacteria and protozoa and their pathogenic role. Behring Inst. Mitt., No.55, 34 (1974)

    Google Scholar 

  91. Neurath, A.R., Hartzell, R.W., Rubin, B.R.: Isoelectric focusing of neuraminidase. Experientia26, 1210 (1970)

    Google Scholar 

  92. Nicolai, H.v., Zilliken, F.: Neuraminidase from bifidobacterium bifidum var. pennsylvanicus. Behring Inst. Mitt., No.55, 78 (1974)

    Google Scholar 

  93. Nordling, S.E., Mayhew, E.: On the intracellular uptake of neuraminidase. Exp. Cell. Res.44, 552 (1966)

    Google Scholar 

  94. Novogrodsky, A., Katchalski, E.: Induction of lymphocyte transformation by sequential treatment with neuraminidase and galactose oxidase. Proc. Nat. Acad. Sci. USA70, 6, 1824 (1973)

    Google Scholar 

  95. Novogrodsky, A.: Potentiation of phytomitogens action by neuraminidase and basic polypeptides. Nature250, 788 (1974)

    Google Scholar 

  96. Novogrodsky, A.: Induction of lymphocyte cytotoxicity by modification of the effector or target cells with periodate or with neuraminidase and galactose oxidase. J. Immunol.114, 3 (1975)

    Google Scholar 

  97. Ohta, N., Pardee, A.B., McAuslan, B.R. et al.: Sialic acid contents and controls of normal and malignant cells. Biochim. Biophys. Acta158, 98 (1968)

    Google Scholar 

  98. Pagano, G., Zarrilli, D., Cajano, A.: Effects of incubation with lysozyme and neuraminidase on tumor cells. Int. Cancer Congress Florence 1974

  99. Pardoe, G.I.: The inducible neuraminidases of pathogenic microorganisms. Behring Inst. Mitt., No.55, 103 (1974)

    Google Scholar 

  100. Porwit-Bobr, Z., Slowik, M., Tomecki, J.: Effect of neuraminidase-treated and mitomycin C-treated polyoma tumor cells on the established tumor growth in CBA mice. I. An attempt at evaluation of polyoma tumor destruction using the distribution of lissamine green method. Folia Histochemica et Cytochemica12, 3–1, 315 (1974)

    Google Scholar 

  101. Prokop, O., Uhlenbruck, G., Kühler, W.: A new source of antibody-like substances having anti-blood group specificity. Vox Sang14, 321 (1968)

    Google Scholar 

  102. Ray, P.K., Gewurz, H., Simmons, R.L.: The mechanism of increased sensitivity of neuraminidase-treated cells to antibody-induced cytolysis. Fed. Proc.29, 573 (1970)

    Google Scholar 

  103. Ray, P.K., Simmons, R.L.: Failure of neuraminidase to unmask allogeneic antigens on cell surface. Proc. Soc. Exp. Biol. Med.138, 600 (1971)

    Google Scholar 

  104. Ray, P.K., Gewurz, H., Simmons, R.L.: Complement sensitivity of neuraminidase-treated lymphoid cells. Transplantation12, 327 (1971)

    Google Scholar 

  105. Ray, P.K., Gewurz, H., Simmons, R.L.: The serologic behaviour of neuraminidase-treated lymphoid cells: Alloantigenicity and complement sensitivity. Clin. exp. Immunol.11, 441 (1972)

    Google Scholar 

  106. Ray, P.K., Simmons, R.L.: Comparative effect of viral and bacterial neuraminidase on the complement sensitivity of lymphoid cells. Clin. and Exp. Immun.10, 139 (1972)

    Google Scholar 

  107. Ray, P.K., Simmons, R.L.: Differential release of sialic acid from normal and malignant cells by Vibrio cholerae neuraminidase or influenza virus neuraminidase. Cancer Res.33, 936 (1973)

    Google Scholar 

  108. Ray, P.K., Challerjee, S.: Neuraminidase treatment enhances the lysolecithin induced intercellular adhesion of Amoeba proteus. Z. Naturforsch.30c, 551 (1975)

    Google Scholar 

  109. Ray, P.K., Sundaram, K.: Neuraminidase induced immunotherapy of cancer. Int. Cancer Congress Florence 1974

  110. Ray, P.K., Thakur, V.S., Sundaram, K.: Antitumor immunity — I. Differential response of neuraminidase-treated and x-irradiated tumor vaccine. Europ. J. Cancer11, 1 (1975)

    Google Scholar 

  111. Ray, P.K., Thakur, V.S., Sundaram, K.: Antitumor immunity. II. Viability, tumorigenicity, and immunogenicity of neuraminidase-treated tumor cells: Effective immunization of animals with a tumor vaccine. J. Natl. Cancer Inst.56, 83 (1976)

    Google Scholar 

  112. Reed, R.C., Gutterman, J.U., Mavligit, G.M., Hersh, E.M.: Sialic acid on leukemia cells: Relation to morphology and tumor immunity (37896). Proc. of the Soc. for Exp. Biol. and Med.145, 790 (1974)

    Google Scholar 

  113. Reisner, E.G., Amos, D.B.: The complement-binding and absorptive capacity of human white blood cells treated with neuraminidase. Transplantation14, 455 (1972)

    Google Scholar 

  114. Reisner, E.G., Flye, K., Su Chung, S., Amos, D.B.: The cytotoxic reactivity and sialic acid content of human lymphoid cells. Tissue Antigens4, 7 (1974)

    Google Scholar 

  115. Reisner, E.G.: Relation of the neuraminidase-revealed antigens of human lymphocytes and erythrocytes. Transplantation19, 359 (1975)

    Google Scholar 

  116. Rios, A., Simmons, R.L.: Comparative effect of mycobacterium bovis-and neuraminidase-treated tumor cells on the growthof established methylcholanthrene fibrosarcomas in syngeneic mice. Cancer Res.3, 16 (1972)

    Google Scholar 

  117. Rios, R., Simmons, R.L.: Active specific immunotherapy of minimal residual tumor: Excision plus neuraminidase-treated tumor cells. Int. J. Cancer13, 71 (1974)

    Google Scholar 

  118. Rogentine, G.N. Jr., Plocinik, B.A.: Carbohydrate inhibition studies of the naturally occurring human antibody to neuraminidase-treated human lymphocytes. J. Immunol.113, 3 (1974)

    Google Scholar 

  119. Rogentine, G.N. Jr.: Naturally occurring human antibody to neuraminidase-treated human lymphocytes. Antibody levels in normal subjects, cancer patients, and subjects with immuno deficiency. J. Natl. Cancer Inst.54, 1307 (1975)

    Google Scholar 

  120. Rosato, F.E., Brown, A.S., Miller, E.E., Rosato, E.F., Mullis, W.F., Johnson, J., Moskovitz, A.: Neuraminidase immunotherapy of tumors in man. Surgery, Gynecology and Obstetrics139, 675 (1974)

    Google Scholar 

  121. Rosato, F.E., Miller, E., Rosato, E., Brown, A., Wallack, M., Johnson, J., Moskovitz, A.: Active specific immunotherapy of human solid tumors. Ann. N.Y. Acad. Sci., in press 1976

  122. Rosenberg, S.A., Rogentine, G.N. Jr.: Natural human antibodies to “hidden” membrane components. Nature (New Biol.)239, 203 (1972)

    Google Scholar 

  123. Rosenberg, S.A., Plocinik, B.A., Rogentine, G.N.: “Unmasking” of human lymphoid cell heteroantigens by neuraminidase treatment. J. Nat. Canc. Inst.48, 1271 (1972)

    Google Scholar 

  124. Rosenberg, S.A., Einstein, A.B.: Sialic acids on the plasma membrane of cultured human lymphoid cells: Chemical aspects and biosynthesis. J. Cell. Biol.53, 466 (1972)

    Google Scholar 

  125. Rosenberg, S.A., Schwartz, S., Baker, A.: Natural antibodies to “cryptic” membrane antigens exposed by treatment with neuraminidase. Behring Inst. Mitt., No.55, 204 (1974)

    Google Scholar 

  126. Rosenberg, S.A., Schwarz, S.: Murine antibodies to a cryptic membrane antigen: Possible explanation for neuraminidase-induced increase in cell immunogenicity. J. Natl. Cancer Int.52, 1151 (1974)

    Google Scholar 

  127. Ruhenstroth-Bauer, G., Fuhrmann, G.F., Gzanzek, E.: Elektrophoretische Untersuchungen an normalen und malignen Zellen. Naturwiss.49, 363 (1962)

    Google Scholar 

  128. Ruhenstroth-Bauer, G., Fuhrmann, G.F., Kübler, W., Rueff, F., Munk, K.: Zur Bedeutung der Neuraminsäuren in der Zellmembran für das Wachstum maligner Zellen. Z. für Krebsforsch.65, 37 (1962)

    Google Scholar 

  129. Sachtleben, P., Gsell, R., Mehrishi, J.N.: Neuraminidase and anti-neuraminidase serum: Effect on the cell surface properties. Vox Sang.25, 519 (1973)

    Google Scholar 

  130. Sanford, B.H.: An alteration in tumor histocompatibility induced by neuraminidase. Transplantation5, 1273 (1967)

    Google Scholar 

  131. Sanford, B.H., Codington, J.F.: Alteration of the tumor cell surface by neuraminidase. Transplantation Proc.3, 1155 (1971)

    Google Scholar 

  132. Sanford, B.H., Codington, J.F.: further studies on the effect of neuraminidase on tumor cell transplantability. Tissue Antigens1, 153 (1971)

    Google Scholar 

  133. Sauter, C., Lindenmann, J., Gerber, A.: Agglutination of leukemic myeloblasts by neuraminidase. Europ. J. Cancer8, 451 (1972)

    Google Scholar 

  134. Schick, H.-J., Schmidtberger, R.: Affinity of Vibrio cholerae neuraminidase to different human sialoglycoproteins. Behring Inst. Mitt., No.55, 123 (1974)

    Google Scholar 

  135. Schlesinger, M., Gottesfeld, S.: The effect of neuraminidase on expression of cellular antigens. Transplant. Proc.3, 1154 (1971)

    Google Scholar 

  136. Schlesinger, M., Amos, D.B.: The effect of neuraminidase on the serological properties of murine lymphoid cells. Transplant. Proc.111, 895 (1971)

    Google Scholar 

  137. Schlesinger, M., Chaouat, M.: The exposure of autoantigenic determinants on the cell surface of murine thymocytes following neuraminidase treatment. Behring Inst. Mitt., No.55, 216 (1974)

    Google Scholar 

  138. Schmidtke, J.R., Simmons, R.L.: Augmented uptake of neuraminidase-treated sheep red blood cells: Participation of Opsonic Factors. J. Natl. Cancer Inst.54, 1379 (1975)

    Google Scholar 

  139. Sedlacek, H.H., Seiler, F.R.: Dose dependency of the effect of syngeneic, Vibrio cholerae-neuraminidase-treated mastocytoma cells on the life span of DBA f/2 mice. Behring Inst. Mitt. No.55, 343 (1974)

    Google Scholar 

  140. Sedlacek, H.H., Seiler, F.R.: Demonstration of Vibrio cholerae neuraminidase (VCN) on the surface of VCN-treated cells. Behring Inst. Mitt., No.55, 254 (1974)

    Google Scholar 

  141. Sedlacek, H.H., Meesmann, H., Seiler, F.R.: Regression of spontaneous mammary tumors of dogs after injection of neuraminidase-treated tumor cells. A preliminary communication. Behring Inst. Mitt., No.55, 349 (1974)

    Google Scholar 

  142. Sedlacek, H.H., Meesmann, H., Seiler, F.R.: Regression of spontaneous mammary tumors in dogs after injection of neuraminidase-treated tumor cells. Int. J. Cancer15, 409 (1975)

    Google Scholar 

  143. Sedlacek, H.H., Johannsen, R., Seiler, F.R.: Neuraminidase: A promising compound for immunomanipulation. Australian Soc. for Immunol.—Annual Meeting 1975, Adelaide, Dec. 8–10, 1975

  144. Sedlacek, H.H., Seiler, F.R.: The spontaneous mammary tumor of dogs: A model for tumor immunotherapy in man. submitted 1976

  145. Sedlacek, H.H., Weise, M., Meesmann, H., Seiler, F.R.: Tumor immunotherapy of canine mammary tumors with the use of neuraminidase-treated tumor cells. In preparation 1977

  146. Seigler, H.F., Shingleton, W.W., Metzgar, R.S., Buckley, C.E., Bergoc, P.M., Miller, D.S., Fetter, B.F., Phaup, M.B.: Nonspecific and specific immunotherapy in patients with melanoma. Surgery72, 1, 162 (1972)

    Google Scholar 

  147. Seiler, F.R., Sedlacek, H.H., Kanzy, E.-J., Lang, W.: Über die Brauchbarkeit immunologischer Nachweismethoden zur Differenzierung funktionell verschiedener Lymphozyten: Spontanrosetten Komplementrezeptorrosetten und Immunglobulinrezeptoren. Behring Inst. Mitt., No.52, 26 (1972)

    Google Scholar 

  148. Seiler, F.R., Sedlacek, H.H.: Alterations of immunological phenomena by neuraminidase: Marked rise in the number of lymphocytes forming rosettes or bearing immunoglobulin receptors. Behring Inst. Mitt., No.55, 258 (1974)

    Google Scholar 

  149. Sethi, K.K., Brandis, H.: In vitro cytotoxicity of normal serum factor(s) on neuraminidase-treated Ehrlich ascites tumor cells and murine leukemia L1210 cells. Z. Immun. Forsch.143, 426 (1972)

    Google Scholar 

  150. Sethi, K.K., Brandis, H.: Neuraminidase induced loss in the transplantability of murine leukaemia L1210, induction of immunoprotection and the transfer of induced immunity to normal DBA/2 mice by serum and peritoneal cells. Br. J. Cancer27, 106 (1973)

    Google Scholar 

  151. Sethi, K.K., Brandis, H.: Synergistic cytotoxic effect of macrophages and normal mouse serum on neuraminidase-treated murine leukaemia cells. Europ. J. Cancer9, 809 (1973)

    Google Scholar 

  152. Simmons, R.L., Rios, A., Ray, P.K.: Mechanism of neuraminidase induced antigen “unmasking”. Surg. Forum21, 265 (1970)

    Google Scholar 

  153. Simmons, R.L., Rios, A., Lundgren, G.: Immunospecific regression of methylcholanthrene fibrosarcoma with the use of neuraminidase. Surgery70, 38 (1971)

    Google Scholar 

  154. Simmons, R.L., Lipschultz, M.L., Rios, A., Ray, P.K.: Failure of neuraminidase to unmask histocompatibility antigens on trophoblast. Nature (New Biol.)231, 111 (1971)

    Google Scholar 

  155. Simmons, R.L., Rios, A., Ray, P.K.: Immunogenicity and antigenicity of lymphoid cells treated with neuraminidase. Nature (Lond.)23, 179 (1971)

    Google Scholar 

  156. Simmons, R.L., Rios, A.: Immunotherapy of cancer: Immunospecific rejection of tumors in recipients of neuraminidase-treated tumor cells plus BCG. Science174, 591 (1971)

    Google Scholar 

  157. Simmons, R.L., Rios, A.: Immunotherapy of cancer: Immunospecific rejection of tumor in recipients of neuraminidase-treated tumor cells plus BCG. Science174, 591 (1971)

    Google Scholar 

  158. Simmons, R.L., Rios, A.: Combined use of BCG and neuraminidase in experimental tumor immunotherapy. Surgical Forum XXII (1971)

  159. Simmons, R.L., Rios, A., Ray, P.K., Lundgren, G.: Effect of neuraminidase on growth of a 3-methylcholanthrene-induced fibrosarcoma in normal and immunosuppressed syngeneic mice. J. Nat. Cancer Inst.47, 5, 1087 (1971)

    Google Scholar 

  160. Simmons, R.L., Rios, A., Lundgren, G., Ray, P.K., McKhann, C.F., Haywood, G.: Immunospecific regression of methylcholanthrene fibrosarcoma using neuraminidase. Surgery70, 38 (1971)

    Google Scholar 

  161. Simmons, R.L., Rios, A., Kersey, J.H.: Regression of spontaneous mammary carcinomas using direct injections of neuraminidase and BCG. J. of Surgical Research12, 57 (1972)

    Google Scholar 

  162. Simmons, R.L., Rios, A.: Immunospecific regression of methylcholanthrene fibrosarcoma with the use of neuraminidase. II. Intratumour injections of neuraminidase. Surgery71, 556 (1972)

    Google Scholar 

  163. Simmons, R.L., Rios, A.: Differential effect of neuraminidase on the immunogenicity of viral associated and private antigens of mammary carcinomas. J. Immunol.111, 1820 (1973)

    Google Scholar 

  164. Simmons, R.L., Rios, A.: Immunospecific regression of methylcholanthrene fibrosarcoma with the use of neuraminidase. V. Quantitative aspects of the experimental immunotherapeutic model. Israel J. Med. Sci.10, 8, 925 (1974)

    Google Scholar 

  165. Simmons, R.L., Rios, A.: Cell surface modification in the treatment of experimental cancer neuraminidase or concanavalin A. Cancer34, 1541 (1974)

    Google Scholar 

  166. Simmons, R.L., Rios, A.: Comparative immunotherapeutic effect of concanavalin A and neuraminidase-treated cancer cells. Transplant. Proc.VII, 2, 247 (1975)

    Google Scholar 

  167. Smith, D.F., Walborg, E.F.: Isolation and chemical characterization of cell surface sialoglycopeptide fractions during progression of rat ascites hepatoma AS-30D. Cancer Res.32, 543 (1972)

    Google Scholar 

  168. Springer, G.F., Desai, P.R., Banatwala, I.: Blood group MN specific substances and precursors in normal and malignant human breast tissues. Naturwiss.61, 457 (1974)

    Google Scholar 

  169. Springer, G.F., Desai, P.R.: Increase in anti-T titer scores of breast-carcinoma patients following mastectomy. Naturwiss.62, 587 (1975)

    Google Scholar 

  170. Springer, G.F., Desai, P.R.: Depression of Thomsen-Friedenreich (anti-T) antibody in humans with breast carcinoma. Naturwiss.62, 302 (1975)

    Google Scholar 

  171. Springer, G.F., Desai, P.R., Banatwala, I.: Brief communication: Blood group MN antigens and precursors in normal and malignant human breat glandular tissue. J. Natl. Cancer Inst.54, 2, 335 (1975)

    Google Scholar 

  172. Thomsen, O.: Ein vermehrungsfähiges Agens als Veränderer des isoagglutinatorischen Verhaltens der roten Blutkörperchen, eine bisher unbekannte Quelle der Fehlbestimmungen. Z. Immun. Forsch.52, 85 (1927)

    Google Scholar 

  173. Tisserand-Jochem, E.-M.: Natural autoantibodies against neuraminidase-treated cells in normal sera and seminal plasma. Behring Inst. Mitt., No.55, 197 (1974)

    Google Scholar 

  174. Tuppy, H.: Preparation, purification activity and specificity of neuraminidases. Behring Inst. Mitt., No.55, 97 (1974)

    Google Scholar 

  175. Uhlenbruck, G., Pardoe, G.I., Bird, G.W.G.: On the specificity of lectins with a broad agglutination spectum. II. Studies on the nature of the T-antigen and the specific receptors of the lectin of Arachis hypogoea (ground-nut). Z. Immun. Forsch.138, 424 (1969)

    Google Scholar 

  176. Uhlenbruck, G., Hermann, W.P.: Agglutination of normal, coated and enzyme-treated human spermatozoa with heterophile agglutinins. Vox Sang.23, 444 (1973)

    Google Scholar 

  177. Uhlenbruck, G., Rothe, A.: Biological alterations of membrane-bound glycoproteins by neuraminidase treatment. Behring Inst. Mitt., No.55, 177 (1974)

    Google Scholar 

  178. Watkins, E. Jr., Ogata, Y., Anderson, L.L., Watkins, E. III., Waters, M.F.: Activation of host lymphocytes cultured with cancer cells treated with neuraminidase. Nature New Biology231, 20, 83 (1971)

    Google Scholar 

  179. Watkins, E., Jr., Gray, B.N., Anderson, L.L., Baralt, O.L., Nebril, L.R., Waters, M.F., Connery, C.K.: Neuraminidase-mediated augmentation of in vitro immune response of patients with solid tumors. Int. J. Cancer14, 799 (1974)

    Google Scholar 

  180. Watkins, E., Jr.: Neuraminidase accentuation of cancer cell immunogenicity. Behring Inst. Mitt., No.55, 355 (1974)

    Google Scholar 

  181. Weiss, L.: Studies on cell deformability. I. Effect of surface charge. J. Cell. Biol.26, 735 (1965)

    Google Scholar 

  182. Weiss, L., Mayhew, E., Ulrich, K.: The effect of neuraminidase on the phagocytic process in human monocytes. Lab. Invest.15, 1304 (1966)

    Google Scholar 

  183. Weiss, L.: Studies on cell adhesion in tissue culture. IX. Electrophoretic mobility and contact phenomena. Exp. Cell Res.51, 609 (1968)

    Google Scholar 

  184. Weiss, L.: Studies on cell deformability. V. Some effects of ribonuclease. J. Theoret. Biol.18, 9 (1968)

    Google Scholar 

  185. Weiss, L., Sinc, L.F.: The electrokinetic surface of human cells of lymphoid origin and their ribonuclease susceptibility. Cancer Res.30, 90 (1970)

    Google Scholar 

  186. Weiss, L., Hauschka, T.S.: Malignancy, electrophoretic mobilities and sialic acids at the electrokinetic surface of TA3 cells. Int. J. Cancer6, 270 (1970)

    Google Scholar 

  187. Weiss, L., Cudney, T.L.: Some effects of neuraminidase on the in vitro interactions between spleen and mastocytoma (P815) cells. Int. J. Cancer7, 187 (1971)

    Google Scholar 

  188. Weiss, L.: Neuraminidase, sialic acids, and cell interactions. J. Nat. Cancer Inst.50, 3 (1973)

    Google Scholar 

  189. Weiss, L., Fisher, B., Fisher, E.R.: Observations on the effect of neuraminidase on the distribution of intravenously injected Walker tumor cells in rats. Cancer34, 680 (1974)

    Google Scholar 

  190. Weiss, L., Glaves, D., Waite, D.A.: The influence of host immunity on the arrest of circulating cancer cells, and its modification by neuraminidase. Int. J. Cancer13, 850 (1974)

    Google Scholar 

  191. Wiig, J.N.: Surface structures influencing the migration in vivo (ecotaxis) of murine thymocytes, T- and B-cells. Acta path. microbiol. scand. Sect. C,84, 59 (1976)

    Google Scholar 

  192. Wilson, R.E., Sonis, S.T., Godrick, E.A.: Neuraminidase as an adjunct in the treatment of residual systemic tumor with specific immune therapy. Behring Inst. Mitt., No.55, 334 (1974)

    Google Scholar 

  193. Winzler, R.J.: Carbohydrates in cell surfaces. Int. Rev. Cytol.29, 77 (1970)

    Google Scholar 

  194. Woodruff, J.J., Gesner, B.M.: The effect of neuraminidase on the fate of transfused lymphocyte. J. exp. Med.129, 551 (1969)

    Google Scholar 

  195. Wunderlich, J.R., Martin, W.J., Fletcher, F.: Enhanced immunogenicity of syngeneic tumor cells coated with concanavalin A. Fed. Proc.30, 246 (1971)

    Google Scholar 

  196. Yuhas, J.M., Toya, R.E., Pazmifio, N.H.: Neuraminidase and cell viability: Failure to detect cytotoxic effects with dye-exclusion techniques. J. Natl. Cancer Inst.53, 465 (1974)

    Google Scholar 

  197. Simmons, R.L.: Comparison of chemotherapy to chemotherapy plus VCN-treated autologous tumor cells in stages II and III melanoma. Int. Meeting on Immunotherapy of Cancer: Present Status of Trials in Man, Oct. 27–29, 1976, N.I.H., Bethesda, Maryland, USA

  198. Holland, J.F.: Comparison of chemotherapy to chemotherapy plus VCN-treated cells in acute myelogeneous leukemia. Int. Meeting on Immunotherapy of Cancer: Present Status of Trials in Man, Oct. 27–29, 1976, N.I.H., Bethesda, Maryland, USA

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    H. H. Sedlacek, F. R. Seiler & H. G. Schwick

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Sedlacek, H.H., Seiler, F.R. & Schwick, H.G. Neuraminidase and tumor immunotherapy. Klin Wochenschr 55, 199–214 (1977). https://doi.org/10.1007/BF01487712

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