Biologic and immunologic therapies for ovarian cancer.
Biologic therapy of ovarian cancer has been conducted using nonspecific biologic response modifiers, cytokines, monoclonal antibodies (MAbs), vaccines, and gene therapy. Antibodies directed toward her2/neu have also been studied. Phase I and II gene therapy trials using adenoviral vectors containing a wild-type or modified p53 have shown that the treatment is well tolerated. Phase II and III trials are ongoing with MAbs directed against CA-125 (MAb B43.13) and an antibody directed against HMFG1 (anti-HMFG1-yttrium-90-labeled antibody). The trials have shown that these agents are well tolerated and that immunologic responses occur, although the ultimate clinical value of these agents remains to be determined. Prolonged survival after MAb B43.13 treatment has been correlated with changes in several immune parameters, including human antimurine antibody, Ab2, anti-CA-125 antibody development, and induced T-cell immunity. Clinical trials using a MAb directed toward the encoded products of her2/neu have shown minimal activity against ovarian cancer in a phase I and II trial conducted by the Gynecologic Oncology Group. Cytokine therapies have been administered systemically and intraperitoneally. Intracavitary interferon alfa, interferon gamma, and interleukin-2 alone or in combination with cytotoxic therapy in phase I and II trials demonstrated intraperitoneal lymphoid cell stimulation and produced antitumor responses. A randomized trial of chemotherapy with or without interferon gamma in primary treatment produced a response and a progression-free survival advantage in the arm that incorporated the interferon gamma, without a statistically significant benefit in overall survival. A phase III study of interferon gamma in combination with first-line chemotherapy is currently ongoing.
Division of Gynecologic Oncology, David Geffen School of Medicine at University of California Los Angeles, UCLA Center for the Health Sciences, Los Angeles, CA 90095-1740, USA. jberek@mednet.ucla.edu
Jonathan S
JS
Berek
Birgit C
BC
Schultes
Christopher F
CF
Nicodemus
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001688:Biological Products / Q000627:therapeutic use*; D018394:CA-125 Antigen / Q000276:immunology; D003131:Combined Modality Therapy; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D007167:Immunotherapy; D016898:Interferon-alpha / Q000627:therapeutic use; D007371:Interferon-gamma / Q000627:therapeutic use; D018396:Mucin-1 / Q000276:immunology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology; D012008:Recurrence; D000068878:Trastuzumab; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D015020:Yttrium Isotopes / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D001688:Biological Products; D018394:CA-125 Antigen; D016898:Interferon-alpha; D007371:Interferon-gamma; D018396:Mucin-1; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D016159:Tumor Suppressor Protein p53; D015020:Yttrium Isotopes; C495901:TP53 protein, human; C469215:pemtumomab; C508053:ERBB2 protein, human; C107428:oregovomab