Screening For Biological Response Modifiers Methods And Rationale

Screening for Biological Response Modifiers: Methods and Rationale

The observation in the 1950s that nitrogen mustard and other toxic chemicals could induce antitumor responses in patients with refractory lymphoma initiated a massive search for active chemotherapeutic agents. The initial observations stimulated a search for new chemotherapeutic agents which might have increased antitumor activity with less toxicity for normal tissues. To aid in the search for these new chemicals and to attempt to distinguish among the many toxic chemicals which might be candidates for clinical studies, the National Cancer Institute, the pharmaceutical industry, and the cancer research laboratories of most Western nations developed systems for "screening" drugs for antitumor activity. Perhaps the most extensive screening program was established by the National Cancer Institute (1). This screening program has evolved over the last two decades, an evolution which has been repeatedly reviewed (2-5). Various screening programs in use have examined over 500,000 compounds as potential anticancer agents. From these, there are now approximately forty anticancer drugs in clinical use. The utiliy of these compounds and their toxicities have been reviewed on many occasions. It is now apparent that more active and less toxic anticancer drugs are needed. It is also clear that the current screening programs are identifying compounds with similar levels of activity and with continuing moderate to severe toxicity (6).

Immunopharmacology Reviews

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.

Immunomodulation of Neoplasia