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Frontiers in immunomodulators
CLINICAL
IMMUNOLOGY
AND
IMMUNOPATHOLOGY
MEETING Frontiers
28, 125-127 (1983)
REPORT
in lmmunomodulators
Viareggio, Italy, May 14-16, 1982
An international symposium centered on the significance and the use of substances with immunomodulating activity was held at Viareggio, Italy, May 1416, 1982. Dr. H. H. Fudenberg of the Medical University of South Carolina, Charleston, was chairman of the symposium, which was organized by Dr. F. Ambrogi of the University of Pisa. The symposium consisted of five sessions, three dealing with biological immunomodulators, the other two with synthetic immunomodulators. Each session was subdivided into groups of reports with different themes. Two poster sessions were also held. In the first session, after Dr. Fudenberg presented a general classification of the currently available immunomodulators, Dr. H. Friedman (Tampa, Fla.) and Dr. M. Bendinelli (Pisa, Italy) reviewed, respectively , “Immunomodulation and Bacterial Antigens” and “Immunomodulation and Viral Infections.” Substances extracted from bacterial cell walls appear to be important modifiers of the immune response, in particular purified extracts like the lipopolysaccharides and lipoteichoic acid. Moreover, probable mechanisms of action of many antiviral agents used as immunomodulators were proposed. Dr. R. Binaghi explained the current problems regarding immunological preparations of antiparasitic vaccines for human use. He also discussed the possible mechanisms of survival of parasites in the host. Dr. D. S. Terman, of Houston, Texas, reported the results of infusion of seven plasmas purified over protein Abearing staphylococci (or purified protein A bound to Collodion charcoal) into humans and dogs bearing breast tumors; he demonstrated by histopathology the destruction of human and dog tumors which were previously nonresponsive to the usual therapy. Another theme was that of the transfer of cell-mediated immunity presented by Dr. R. Paganelli of Rome, Italy, and Dr. H. H. Fudenberg of Charleston, South Carolina. Dr. Fudenberg discussed particular aspects of the identification of the molecular structure of the various factors implicated in the transfer of immunity by dialyzable leukocyte extracts (DLE). This method of immunotherapy and immunoprophylaxis gave striking long-range results in the treatment of human acquired and congenital T-cell immunodeficiencies when donors were selected by immunologic test, when the DLE was pretested for potency in vitro with the cells of the putative recipient, and when the response to therapy was monitored by immunological tests. In the same session, Dr. J. Mannick of Boston, Massachusetts, outlined experimental and clinical results obtained in the treatment of tumors using immune RNA. Remissions were obtained in treatment of 125 0090-1229/83 $1.50 Copyri&t AU rights
@ 1983 by Academic Press. Inc. of reproduction in any form reserved.
126
MEETING
REPORT
renal cell carcinoma and recurrent melanoma after injection of autologous lymphocytes, previously incubated with immune RNA, obtained from animals immunized by the tumor to be treated. In the second session, also dedicated to the biological immunomodulators, Dr. A. Marmont of Genoa, Italy, and Dr. R. Good of Oklahoma City, Oklahoma, presented reports on immunodeficiency diseases as well as research on those states of hematologic pathology, such as leukemias, aplastic anemias, and others. These pathological conditions can respond to immunosuppressive treatment or to transplantation of fetal liver or bone marrow. At the same time, they outlined the problems peculiar to these therapies. Dr. U. Bocci of Siena, Italy, and Dr. M. Tovey of Villejuif, France, described the characteristics of the interferon system and its potential therapeutic uses, mainly in the field of tumors. Dr. F. Aiuti of Rome, Italy, Dr. L. Chatenoud of Paris, France, and Dr. G. Corte of Genoa, Italy, dealt with the impact of monoclonal antibodies on current immunological understanding and their potential use in immunotherapy and immunoprophylaxis (e.g., prevention of rejection of renal transplants). The third session of the symposium dealt with the importance of thymic function in the maintenance of immune function. The first of two reports reviewed “interleukins” and other soluble substances necessary for T-T cell interaction; their immunopharmacological uses were presented by Dr. M. Piantelli of Rome, Italy, and Dr. M. Kronke of Mainz, West Germany. Numerous speakers, M. Dardenne (Paris, France), S. Davis (East Orange, N.J.), M. G. Bernengo (Torino, Italy), N. Hall (Washington, D.C.), J. L. Touraine (Lyon, France), A. S. Klein (Ramat Gan, Israel), and M. Fiorilli (Rome, Italy), dealt with the problem of the clinical use and the “in vitro” and “in viva” evaluation of the thymic hormones. It appears that these thymic-derived substances are of great value in the adjuvant therapy of some malignant diseases and severe congenital or acquired immunodeficiency states. The fourth session dealt with synthetic chemical products possessing immunomodulating properties. The session opened with a group of reports that described the properties, the characteristics, the methods of evaluation, and the clinical experience of Isoprinosine; this is an inosine-containing compound and has created interest as both an antiviral agent and immunomodulator. Specificitally, J. Hadden (New York, N.Y.), J. Wybran (Brussels, Belgium), C. De Simone (Rome, Italy), and M. Galli (Milan, Italy) spoke of Methisoprinol (Viruxan, Isoprinosine, Inosiplex) and their experimental and clinical results in reversing viral- and cancer-induced T-cell immunosuppression. Dr. S. Del Giacco of Cagliari, Italy, analyzed the characteristics and the clinical use of Levamisole, an antihelminthic agent with immunomodulating properties. In this same session, Dr. Spreafico of Milan, Italy, introduced the concept of immunotoxicology as the “study of the phenomena of the alterations of the immunological apparatus by different chemical substances and the immunological methods used to demonstrate these changes.” In the fifth and last session, Dr. S. Dray of Chicago, Illinois, reported con-
MEETING REPORT
127
cerning cyclophosphamide and its immunomodulating properties. This compound, used traditionally in antitumor chemotherapy, can at certain doses be an immunostimulant in that it destroys suppressor immunocytes. It causes immunologically induced tumor regression in a mouse model and may warrant use in such low doses in certain human malignancies. Drs. A. Tagliabue of Siena, Italy, and T. Strom of Boston, Massachusetts, reported on the mechanisms of action of Cyclosporin-A, whose selective toxic effects on T lymphocytes and the interleukins make it an interesting choice as an immunosuppressor in the field of organ transplantation. Finally, Dr. J. Van Laarhoven of Nijmegen, Holland, and Dr. H. Prentice of London, England, treated the relationships between purine metabolism and immunological functions. New means of evaluating these functions and a new system of immunomodulation can be based on the evaluation of certain enzymes, such as adenosine deaminase and their inhibition. F. AMBROGI J. WYBRAN Received December 14, 1982; accepted December 16, 1982
IMMUNOLOGY
AND
IMMUNOPATHOLOGY
MEETING Frontiers
28, 125-127 (1983)
REPORT
in lmmunomodulators
Viareggio, Italy, May 14-16, 1982
An international symposium centered on the significance and the use of substances with immunomodulating activity was held at Viareggio, Italy, May 1416, 1982. Dr. H. H. Fudenberg of the Medical University of South Carolina, Charleston, was chairman of the symposium, which was organized by Dr. F. Ambrogi of the University of Pisa. The symposium consisted of five sessions, three dealing with biological immunomodulators, the other two with synthetic immunomodulators. Each session was subdivided into groups of reports with different themes. Two poster sessions were also held. In the first session, after Dr. Fudenberg presented a general classification of the currently available immunomodulators, Dr. H. Friedman (Tampa, Fla.) and Dr. M. Bendinelli (Pisa, Italy) reviewed, respectively , “Immunomodulation and Bacterial Antigens” and “Immunomodulation and Viral Infections.” Substances extracted from bacterial cell walls appear to be important modifiers of the immune response, in particular purified extracts like the lipopolysaccharides and lipoteichoic acid. Moreover, probable mechanisms of action of many antiviral agents used as immunomodulators were proposed. Dr. R. Binaghi explained the current problems regarding immunological preparations of antiparasitic vaccines for human use. He also discussed the possible mechanisms of survival of parasites in the host. Dr. D. S. Terman, of Houston, Texas, reported the results of infusion of seven plasmas purified over protein Abearing staphylococci (or purified protein A bound to Collodion charcoal) into humans and dogs bearing breast tumors; he demonstrated by histopathology the destruction of human and dog tumors which were previously nonresponsive to the usual therapy. Another theme was that of the transfer of cell-mediated immunity presented by Dr. R. Paganelli of Rome, Italy, and Dr. H. H. Fudenberg of Charleston, South Carolina. Dr. Fudenberg discussed particular aspects of the identification of the molecular structure of the various factors implicated in the transfer of immunity by dialyzable leukocyte extracts (DLE). This method of immunotherapy and immunoprophylaxis gave striking long-range results in the treatment of human acquired and congenital T-cell immunodeficiencies when donors were selected by immunologic test, when the DLE was pretested for potency in vitro with the cells of the putative recipient, and when the response to therapy was monitored by immunological tests. In the same session, Dr. J. Mannick of Boston, Massachusetts, outlined experimental and clinical results obtained in the treatment of tumors using immune RNA. Remissions were obtained in treatment of 125 0090-1229/83 $1.50 Copyri&t AU rights
@ 1983 by Academic Press. Inc. of reproduction in any form reserved.
126
MEETING
REPORT
renal cell carcinoma and recurrent melanoma after injection of autologous lymphocytes, previously incubated with immune RNA, obtained from animals immunized by the tumor to be treated. In the second session, also dedicated to the biological immunomodulators, Dr. A. Marmont of Genoa, Italy, and Dr. R. Good of Oklahoma City, Oklahoma, presented reports on immunodeficiency diseases as well as research on those states of hematologic pathology, such as leukemias, aplastic anemias, and others. These pathological conditions can respond to immunosuppressive treatment or to transplantation of fetal liver or bone marrow. At the same time, they outlined the problems peculiar to these therapies. Dr. U. Bocci of Siena, Italy, and Dr. M. Tovey of Villejuif, France, described the characteristics of the interferon system and its potential therapeutic uses, mainly in the field of tumors. Dr. F. Aiuti of Rome, Italy, Dr. L. Chatenoud of Paris, France, and Dr. G. Corte of Genoa, Italy, dealt with the impact of monoclonal antibodies on current immunological understanding and their potential use in immunotherapy and immunoprophylaxis (e.g., prevention of rejection of renal transplants). The third session of the symposium dealt with the importance of thymic function in the maintenance of immune function. The first of two reports reviewed “interleukins” and other soluble substances necessary for T-T cell interaction; their immunopharmacological uses were presented by Dr. M. Piantelli of Rome, Italy, and Dr. M. Kronke of Mainz, West Germany. Numerous speakers, M. Dardenne (Paris, France), S. Davis (East Orange, N.J.), M. G. Bernengo (Torino, Italy), N. Hall (Washington, D.C.), J. L. Touraine (Lyon, France), A. S. Klein (Ramat Gan, Israel), and M. Fiorilli (Rome, Italy), dealt with the problem of the clinical use and the “in vitro” and “in viva” evaluation of the thymic hormones. It appears that these thymic-derived substances are of great value in the adjuvant therapy of some malignant diseases and severe congenital or acquired immunodeficiency states. The fourth session dealt with synthetic chemical products possessing immunomodulating properties. The session opened with a group of reports that described the properties, the characteristics, the methods of evaluation, and the clinical experience of Isoprinosine; this is an inosine-containing compound and has created interest as both an antiviral agent and immunomodulator. Specificitally, J. Hadden (New York, N.Y.), J. Wybran (Brussels, Belgium), C. De Simone (Rome, Italy), and M. Galli (Milan, Italy) spoke of Methisoprinol (Viruxan, Isoprinosine, Inosiplex) and their experimental and clinical results in reversing viral- and cancer-induced T-cell immunosuppression. Dr. S. Del Giacco of Cagliari, Italy, analyzed the characteristics and the clinical use of Levamisole, an antihelminthic agent with immunomodulating properties. In this same session, Dr. Spreafico of Milan, Italy, introduced the concept of immunotoxicology as the “study of the phenomena of the alterations of the immunological apparatus by different chemical substances and the immunological methods used to demonstrate these changes.” In the fifth and last session, Dr. S. Dray of Chicago, Illinois, reported con-
MEETING REPORT
127
cerning cyclophosphamide and its immunomodulating properties. This compound, used traditionally in antitumor chemotherapy, can at certain doses be an immunostimulant in that it destroys suppressor immunocytes. It causes immunologically induced tumor regression in a mouse model and may warrant use in such low doses in certain human malignancies. Drs. A. Tagliabue of Siena, Italy, and T. Strom of Boston, Massachusetts, reported on the mechanisms of action of Cyclosporin-A, whose selective toxic effects on T lymphocytes and the interleukins make it an interesting choice as an immunosuppressor in the field of organ transplantation. Finally, Dr. J. Van Laarhoven of Nijmegen, Holland, and Dr. H. Prentice of London, England, treated the relationships between purine metabolism and immunological functions. New means of evaluating these functions and a new system of immunomodulation can be based on the evaluation of certain enzymes, such as adenosine deaminase and their inhibition. F. AMBROGI J. WYBRAN Received December 14, 1982; accepted December 16, 1982