Serotherapy of ovarian cancer.
The development of monoclonal antibodies has permitted the identification of several ovarian-tumor-associated antigens which might serve as targets for serotherapy in vivo. With the exception of antibodies directed against growth factor receptors, unmodified monoclonal reagents must activate complement (C') components or bind effector cells to destroy tumor targets. Antibody-dependent cell-mediated cytotoxicity (ADCC) may be particularly important for eliminating tumor cells in vivo. A shortage of functionally active effector cells can limit the efficacy of serotherapy with heteroantisera or monoclonal reagents. The use of immunostimulants such as Corynebacterium parvum has increased the number and activity of effector cells for ADCC within the peritoneal compartment of mice and of patients with ovarian cancer. Intraperitoneal serotherapy can achieve direct contact between antibody and microscopic deposits of ovarian tumor cells which persist following cytoreductive operations and cytotoxic chemotherapy. Conjugation of monoclonal antibodies with radionuclides, drugs or toxins might increase the potency of serotherapy and circumvent the effector shortage. Clinical studies to date have evaluated radionuclide conjugates for imaging and for therapy. Patients with a small volume of disease have responded to treatment. Preclinical models suggest that drug and toxin conjugates might also prove active. Recent studies have demonstrated a synergistic interaction between different immunotoxins. Ovarian carcinoma is likely to be a valuable clinical model for evaluating immunoconjugates which react with epithelial tumor cells.
Lidor
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Department of Medicine, Duke University Medical Center, Durham, N.C.
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000912:Antibodies, Neoplasm / Q000008:administration & dosage; D000920:Antibody-Dependent Cell Cytotoxicity; D000951:Antigens, Neoplasm; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D007167:Immunotherapy; D000922:Immunotoxins / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000276:immunology / Q000628:therapy*; D011425:Propionibacterium acnes / Q000276:immunology
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D000922:Immunotoxins