The goal of the proposed phase II research is to demonstrate a completely novel approach to the treatment of disseminated mycoses and a new application of the concept of antibody-directed activation of prodrugs, which has previously been applied only to cancer chemotherapy. An antibody-directed enzyme prodrug activation system will be developed for activation of the novel prodrug of amphotericin B prepared in Phase I research. Life threatening deep-seated fungal infections are the most common complications seen in AIDS and cancer chemotherapy patients. Others in this high risk category include leukemic patients, iv drug abusers, diabetics, severe burn patients, transplant recipients, and individuals with indwelling catheters. Ironically, it is because of the advent of medical advances in the use of antibiotics, chemotherapeutics, immunosuppressive agents, and steroids that there has been an increase in the number of potential target patients for opportunistic fungal infection. As a result, the incidence of infection of opportunistic mycoses is increasing and has become a major health concern in hospital care.
This is a novel therapy with no precedented commercial applications in existence. The success of liposomal amphotericin B has generated interest in applications of amphotericin B with reduced side effects. Given the status of amphotericin B as the first and last line of defense against life-threatening disseminated mycoses, any improvement in the administration of the drug will be welcomed by the medical profession.
