In anticipation of the opening of the H. Lee Moffitt Cancer Center and Research lnstitut~ on the campus of the University of South Florida, an international symposium, "The First Annual H. Lee Moffitt Symposium on Cancer Biology and Therapeutics" was held in Tampa, Florida on January 20-22, 1986. In this first symposium we decided to present a broad-based series of topics dealing with the major issues in the field of cancer. These topics ranged from the biochemistry of the cancer cell to the design of antineoplastic agents, through tumor cell heterogeneity, treatment of ltuman neoplasms to immunological aspects of cancer biology and tr~atment. The speakers chosen represented individuals of international acclaim who are very active in the area of cancer research and treatment. The symposium brought together scien­ tists/physicians from six nations including Austria, Canada, France, Hungary, West Germany, and of course, the United States. The congeniality of the participants promoted the friendly exchange of knowledge which, it is hoped, will greatly hasten the time when successful management of human cancer will become routine. Future symposia in this series will be highly focused and will deal with a single facet of this vast field of cancer research and treatment. Joseph G. Cory, Editor Andor Szentivanyi, Editor University of South Florida, 1986 V ACKNOWLEDGMENTS This volume presents the Proceedings of the H. Lee Moffitt International Syn~osium on Cancer Biology and Therapeutics which was held in Tampa, Florida on January 20, 21, and 22, 1986.

This publication is based on a Symposium that has been held in Clearwater, Florida on February 19-21, 1986, on antibodies, their structure, synthesis, function, and clinical applicability in disease. Organization of this symposium by the University of South Florida College of Medicine was prompted by the unparalleled current expansion of information on these topics in general, and in the field of antibody diver­ sity, in particular. The issues that surround the last named dimension of this field, began to surface in the late 1950's with the first conclusive genetic studies having been answered, and a new set of concepts has been de­ fined. As we see it from the material presented in this volume, now new and different questions are being raised and answered by studies in progress, and it may be expected that there will be other questions that will be with us for a considerably longer time. We believe that the symposium brought together many prominent investi­ gators with different backgrounds and training experiences such as immunolo­ gists, microbiologists, biochemists, molecular biologists, and clinical sci­ entists, thus providing an excellent example of the interdisciplinary value of modern immunology and modern biomedical science in general. We believe, therefore, that bringing these complex topics to a wide audience of bio­ medical scientists through this symposium as well as this volume is of value to the scientific and to the medical community.

Endotoxins are constituents of all gram negative bacteria, as well as many other microorganisms. Since their original discovery and study at the beginning and middle parts of this century, many investigations have been performed concerning their immunochemistry and physicochemistry, as well as their pharmacologic activities and physiologic effects on the host. It became widely recognized during the beginning of this century that the pyrogenicity of many microbial infections may be associated with endotoxins. Furthermore, some 80 years ago, attempts were begun to "treat" a variety of illnesses including neoplasia, with such "pyrogens", Le. , bacterial endo­ toxins. Inconclusive results were observed including some detrimental ones as well as, in some cases, beneficial ones. It became widely accepted that during infections with many gram negative organisms the fever occurring in patients, as well as many of the untoward pathophysiological effects of the infections, seemed to be due to the endotoxin the bacteria contained or released. In this regard, septic shock has been studied in detail by many clinicians, physiologists and pharmacologists and attempts have been made to relate the devastating effects of infection on metabolic and physiologic alterations caused by endotoxins. Recently, however, many beneficial effects of endotoxin have also been studied.

''A thoroughly enjoyable and very useful work. As the editors say in their preface, ''we have intended these reviews to be the best by the best''-they make this point very convincingly.'' -ASM News, from a review of Volume 1 This series continues to present the most current findings in the field of immune manipulation. Here, twelve chapters provide detailed coverage of cancer, microbial, and allergy immunopharmacology as well as autoimmunity and neuroimmunomodulation.

This publication is based on a Symposium that has been held in Clearwater, Florida on February 19-21, 1986, on antibodies, their structure, synthesis, function, and clinical applicability in disease. Organization of this symposium by the University of South Florida College of Medicine was prompted by the unparalleled current expansion of information on these topics in general, and in the field of antibody diver­ sity, in particular. The issues that surround the last named dimension of this field, began to surface in the late 1950''s with the first conclusive genetic studies having been answered, and a new set of concepts has been de­ fined. As we see it from the material presented in this volume, now new and different questions are being raised and answered by studies in progress, and it may be expected that there will be other questions that will be with us for a considerably longer time. We believe that the symposium brought together many prominent investi­ gators with different backgrounds and training experiences such as immunolo­ gists, microbiologists, biochemists, molecular biologists, and clinical sci­ entists, thus providing an excellent example of the interdisciplinary value of modern immunology and modern biomedical science in general. We believe, therefore, that bringing these complex topics to a wide audience of bio­ medical scientists through this symposium as well as this volume is of value to the scientific and to the medical community.

Endotoxins are constituents of all gram negative bacteria, as well as many other microorganisms. Since their original discovery and study at the beginning and middle parts of this century, many investigations have been performed concerning their immunochemistry and physicochemistry, as well as their pharmacologic activities and physiologic effects on the host. It became widely recognized during the beginning of this century that the pyrogenicity of many microbial infections may be associated with endotoxins. Furthermore, some 80 years ago, attempts were begun to "treat" a variety of illnesses including neoplasia, with such "pyrogens", Le. , bacterial endo­ toxins. Inconclusive results were observed including some detrimental ones as well as, in some cases, beneficial ones. It became widely accepted that during infections with many gram negative organisms the fever occurring in patients, as well as many of the untoward pathophysiological effects of the infections, seemed to be due to the endotoxin the bacteria contained or released. In this regard, septic shock has been studied in detail by many clinicians, physiologists and pharmacologists and attempts have been made to relate the devastating effects of infection on metabolic and physiologic alterations caused by endotoxins. Recently, however, many beneficial effects of endotoxin have also been studied.

'A thoroughly enjoyable and very useful work. As the editors say in their preface, 'we have intended these reviews to be the best by the best'-they make this point very convincingly.' -ASM News, from a review of Volume 1 This series continues to present the most current findings in the field of immune manipulation. Here, twelve chapters provide detailed coverage of cancer, microbial, and allergy immunopharmacology as well as autoimmunity and neuroimmunomodulation.

Immunopharmacology as a field of scientific endeavor had its origins more than thirty years ago in the application of antibody-based techniques to assays of hormones and drugs in tissues and body fluids. More recently, the field has been redefined to include a primary focus on the immune system as a target of xenobiotic action. Advances in the field of immunology have made it apparent that the immune system, like other organ systems, declines in its function as a result of aging, viral infections like AIDS, and other immunotoxic influences, giving rise to secondary immunodeficiency. Deficiencyof the immune system in turn leads to infections, autoimmune diseases, and an increased incidence of certain cancers. The notion of treating the failing immune system is relatively new; however, more than a decade of research on cancer and AIDS has created the burgeoning new clinical field of immunotherapy. Immunopharmacology then stands as the preclinical and clinical science of immune manipulation. As such, like its parent field of pharmacology, it includes within its scope basic studies of immune mechanisms as they relate to the pathogenesis of inflammation and immunologic disturbances. As with pharma­ cology, the perspective is always a therapeutic one. Studies of immune and inflammatory processes emphasize the use of pharmacologic probes and drugs to elucidate the underlying biochemical pharmacology.

Immunopharmacology as a field of scientific endeavor had its origins more than thirty years ago in the application of antibody-based techniques to assays of hormones and drugs in tissues and body fluids. More recently, the field has been redefined to include a primary focus on the immune system as a target of xenobiotic action. Advances in the field of immunology have made it apparent that the immune system, like other organ systems, declines in its function as a result of aging, viral infections like AIDS, and other immunotoxic influences, giving rise to secondary immunodeficiency. Deficiencyof the immune system in turn leads to infections, autoimmune diseases, and an increased incidence of certain cancers. The notion of treating the failing immune system is relatively new; however, more than a decade of research on cancer and AIDS has created the burgeoning new clinical field of immunotherapy. Immunopharmacology then stands as the preclinical and clinical science of immune manipulation. As such, like its parent field of pharmacology, it includes within its scope basic studies of immune mechanisms as they relate to the pathogenesis of inflammation and immunologic disturbances. As with pharma­ cology, the perspective is always a therapeutic one. Studies of immune and inflammatory processes emphasize the use of pharmacologic probes and drugs to elucidate the underlying biochemical pharmacology.

In anticipation of the opening of the H. Lee Moffitt Cancer Center and Research lnstitut~ on the campus of the University of South Florida, an international symposium, "The First Annual H. Lee Moffitt Symposium on Cancer Biology and Therapeutics" was held in Tampa, Florida on January 20-22, 1986. In this first symposium we decided to present a broad-based series of topics dealing with the major issues in the field of cancer. These topics ranged from the biochemistry of the cancer cell to the design of antineoplastic agents, through tumor cell heterogeneity, treatment of ltuman neoplasms to immunological aspects of cancer biology and tr~atment. The speakers chosen represented individuals of international acclaim who are very active in the area of cancer research and treatment. The symposium brought together scien­ tists/physicians from six nations including Austria, Canada, France, Hungary, West Germany, and of course, the United States. The congeniality of the participants promoted the friendly exchange of knowledge which, it is hoped, will greatly hasten the time when successful management of human cancer will become routine. Future symposia in this series will be highly focused and will deal with a single facet of this vast field of cancer research and treatment. Joseph G. Cory, Editor Andor Szentivanyi, Editor University of South Florida, 1986 V ACKNOWLEDGMENTS This volume presents the Proceedings of the H. Lee Moffitt International Syn~osium on Cancer Biology and Therapeutics which was held in Tampa, Florida on January 20, 21, and 22, 1986.

In anticipation of the opening of the H. Lee Moffitt Cancer Center and Research lnstitut~ on the campus of the University of South Florida, an international symposium, "The First Annual H. Lee Moffitt Symposium on Cancer Biology and Therapeutics" was held in Tampa, Florida on January 20-22, 1986. In this first symposium we decided to present a broad-based series of topics dealing with the major issues in the field of cancer. These topics ranged from the biochemistry of the cancer cell to the design of antineoplastic agents, through tumor cell heterogeneity, treatment of ltuman neoplasms to immunological aspects of cancer biology and tr~atment. The speakers chosen represented individuals of international acclaim who are very active in the area of cancer research and treatment. The symposium brought together scien­ tists/physicians from six nations including Austria, Canada, France, Hungary, West Germany, and of course, the United States. The congeniality of the participants promoted the friendly exchange of knowledge which, it is hoped, will greatly hasten the time when successful management of human cancer will become routine. Future symposia in this series will be highly focused and will deal with a single facet of this vast field of cancer research and treatment. Joseph G. Cory, Editor Andor Szentivanyi, Editor University of South Florida, 1986 V ACKNOWLEDGMENTS This volume presents the Proceedings of the H. Lee Moffitt International Syn~osium on Cancer Biology and Therapeutics which was held in Tampa, Florida on January 20, 21, and 22, 1986.

This publication is based on a Symposium that has been held in Clearwater, Florida on February 19-21, 1986, on antibodies, their structure, synthesis, function, and clinical applicability in disease. Organization of this symposium by the University of South Florida College of Medicine was prompted by the unparalleled current expansion of information on these topics in general, and in the field of antibody diver­ sity, in particular. The issues that surround the last named dimension of this field, began to surface in the late 1950's with the first conclusive genetic studies having been answered, and a new set of concepts has been de­ fined. As we see it from the material presented in this volume, now new and different questions are being raised and answered by studies in progress, and it may be expected that there will be other questions that will be with us for a considerably longer time. We believe that the symposium brought together many prominent investi­ gators with different backgrounds and training experiences such as immunolo­ gists, microbiologists, biochemists, molecular biologists, and clinical sci­ entists, thus providing an excellent example of the interdisciplinary value of modern immunology and modern biomedical science in general. We believe, therefore, that bringing these complex topics to a wide audience of bio­ medical scientists through this symposium as well as this volume is of value to the scientific and to the medical community.

Endotoxins are constituents of all gram negative bacteria, as well as many other microorganisms. Since their original discovery and study at the beginning and middle parts of this century, many investigations have been performed concerning their immunochemistry and physicochemistry, as well as their pharmacologic activities and physiologic effects on the host. It became widely recognized during the beginning of this century that the pyrogenicity of many microbial infections may be associated with endotoxins. Furthermore, some 80 years ago, attempts were begun to "treat" a variety of illnesses including neoplasia, with such "pyrogens", Le. , bacterial endo­ toxins. Inconclusive results were observed including some detrimental ones as well as, in some cases, beneficial ones. It became widely accepted that during infections with many gram negative organisms the fever occurring in patients, as well as many of the untoward pathophysiological effects of the infections, seemed to be due to the endotoxin the bacteria contained or released. In this regard, septic shock has been studied in detail by many clinicians, physiologists and pharmacologists and attempts have been made to relate the devastating effects of infection on metabolic and physiologic alterations caused by endotoxins. Recently, however, many beneficial effects of endotoxin have also been studied.

''A thoroughly enjoyable and very useful work. As the editors say in their preface, ''we have intended these reviews to be the best by the best''-they make this point very convincingly.'' -ASM News, from a review of Volume 1 This series continues to present the most current findings in the field of immune manipulation. Here, twelve chapters provide detailed coverage of cancer, microbial, and allergy immunopharmacology as well as autoimmunity and neuroimmunomodulation.

This publication is based on a Symposium that has been held in Clearwater, Florida on February 19-21, 1986, on antibodies, their structure, synthesis, function, and clinical applicability in disease. Organization of this symposium by the University of South Florida College of Medicine was prompted by the unparalleled current expansion of information on these topics in general, and in the field of antibody diver­ sity, in particular. The issues that surround the last named dimension of this field, began to surface in the late 1950''s with the first conclusive genetic studies having been answered, and a new set of concepts has been de­ fined. As we see it from the material presented in this volume, now new and different questions are being raised and answered by studies in progress, and it may be expected that there will be other questions that will be with us for a considerably longer time. We believe that the symposium brought together many prominent investi­ gators with different backgrounds and training experiences such as immunolo­ gists, microbiologists, biochemists, molecular biologists, and clinical sci­ entists, thus providing an excellent example of the interdisciplinary value of modern immunology and modern biomedical science in general. We believe, therefore, that bringing these complex topics to a wide audience of bio­ medical scientists through this symposium as well as this volume is of value to the scientific and to the medical community.

Endotoxins are constituents of all gram negative bacteria, as well as many other microorganisms. Since their original discovery and study at the beginning and middle parts of this century, many investigations have been performed concerning their immunochemistry and physicochemistry, as well as their pharmacologic activities and physiologic effects on the host. It became widely recognized during the beginning of this century that the pyrogenicity of many microbial infections may be associated with endotoxins. Furthermore, some 80 years ago, attempts were begun to "treat" a variety of illnesses including neoplasia, with such "pyrogens", Le. , bacterial endo­ toxins. Inconclusive results were observed including some detrimental ones as well as, in some cases, beneficial ones. It became widely accepted that during infections with many gram negative organisms the fever occurring in patients, as well as many of the untoward pathophysiological effects of the infections, seemed to be due to the endotoxin the bacteria contained or released. In this regard, septic shock has been studied in detail by many clinicians, physiologists and pharmacologists and attempts have been made to relate the devastating effects of infection on metabolic and physiologic alterations caused by endotoxins. Recently, however, many beneficial effects of endotoxin have also been studied.

'A thoroughly enjoyable and very useful work. As the editors say in their preface, 'we have intended these reviews to be the best by the best'-they make this point very convincingly.' -ASM News, from a review of Volume 1 This series continues to present the most current findings in the field of immune manipulation. Here, twelve chapters provide detailed coverage of cancer, microbial, and allergy immunopharmacology as well as autoimmunity and neuroimmunomodulation.

Immunopharmacology as a field of scientific endeavor had its origins more than thirty years ago in the application of antibody-based techniques to assays of hormones and drugs in tissues and body fluids. More recently, the field has been redefined to include a primary focus on the immune system as a target of xenobiotic action. Advances in the field of immunology have made it apparent that the immune system, like other organ systems, declines in its function as a result of aging, viral infections like AIDS, and other immunotoxic influences, giving rise to secondary immunodeficiency. Deficiencyof the immune system in turn leads to infections, autoimmune diseases, and an increased incidence of certain cancers. The notion of treating the failing immune system is relatively new; however, more than a decade of research on cancer and AIDS has created the burgeoning new clinical field of immunotherapy. Immunopharmacology then stands as the preclinical and clinical science of immune manipulation. As such, like its parent field of pharmacology, it includes within its scope basic studies of immune mechanisms as they relate to the pathogenesis of inflammation and immunologic disturbances. As with pharma­ cology, the perspective is always a therapeutic one. Studies of immune and inflammatory processes emphasize the use of pharmacologic probes and drugs to elucidate the underlying biochemical pharmacology.

Immunopharmacology as a field of scientific endeavor had its origins more than thirty years ago in the application of antibody-based techniques to assays of hormones and drugs in tissues and body fluids. More recently, the field has been redefined to include a primary focus on the immune system as a target of xenobiotic action. Advances in the field of immunology have made it apparent that the immune system, like other organ systems, declines in its function as a result of aging, viral infections like AIDS, and other immunotoxic influences, giving rise to secondary immunodeficiency. Deficiencyof the immune system in turn leads to infections, autoimmune diseases, and an increased incidence of certain cancers. The notion of treating the failing immune system is relatively new; however, more than a decade of research on cancer and AIDS has created the burgeoning new clinical field of immunotherapy. Immunopharmacology then stands as the preclinical and clinical science of immune manipulation. As such, like its parent field of pharmacology, it includes within its scope basic studies of immune mechanisms as they relate to the pathogenesis of inflammation and immunologic disturbances. As with pharma­ cology, the perspective is always a therapeutic one. Studies of immune and inflammatory processes emphasize the use of pharmacologic probes and drugs to elucidate the underlying biochemical pharmacology.

In anticipation of the opening of the H. Lee Moffitt Cancer Center and Research lnstitut~ on the campus of the University of South Florida, an international symposium, "The First Annual H. Lee Moffitt Symposium on Cancer Biology and Therapeutics" was held in Tampa, Florida on January 20-22, 1986. In this first symposium we decided to present a broad-based series of topics dealing with the major issues in the field of cancer. These topics ranged from the biochemistry of the cancer cell to the design of antineoplastic agents, through tumor cell heterogeneity, treatment of ltuman neoplasms to immunological aspects of cancer biology and tr~atment. The speakers chosen represented individuals of international acclaim who are very active in the area of cancer research and treatment. The symposium brought together scien­ tists/physicians from six nations including Austria, Canada, France, Hungary, West Germany, and of course, the United States. The congeniality of the participants promoted the friendly exchange of knowledge which, it is hoped, will greatly hasten the time when successful management of human cancer will become routine. Future symposia in this series will be highly focused and will deal with a single facet of this vast field of cancer research and treatment. Joseph G. Cory, Editor Andor Szentivanyi, Editor University of South Florida, 1986 V ACKNOWLEDGMENTS This volume presents the Proceedings of the H. Lee Moffitt International Syn~osium on Cancer Biology and Therapeutics which was held in Tampa, Florida on January 20, 21, and 22, 1986.