Open AccessBiology and therapy with biologic agents in gynecologic cancer
Author(s) -
Jon R. Wiener,
Andrew Berchuck,
Robert C. Bast
Publication year - 1992
Publication title -
current opinion in oncology/current opinion in oncology, with cancerlit
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.297
H-Index - 95
eISSN - 1080-8140
pISSN - 1040-8746
DOI - 10.1097/00001622-199210000-00020
Subject(s) - ovarian cancer , cancer research , medicine , tumor necrosis factor alpha , cytotoxic t cell , pseudomonas exotoxin , ovarian tumor , immunology , interferon , immunotherapy , cancer , biology , cytotoxicity , immune system , in vitro , biochemistry
Growth of epithelial ovarian cancer is influenced by several factors including transforming growth factor-alpha and transforming growth factor-beta, macrophage colony stimulating factor, tumor necrosis factor-alpha, interleukin-1 and interleukin-6, c-erb B-2 (HER-2/neu), and mutant p53. Continued expression of the epidermal growth factor receptor, new expression of c-fms, and overexpression of HER-2/neu are associated with a poor prognosis. A number of cytokines have been used to treat patients with ovarian cancer, including interferon-alpha, interferon-gamma, tumor necrosis factor-alpha, and interleukin-2. Judging from preclinical models, interferon-gamma may be more active than interferon-alpha against human ovarian cancer. Although tumor necrosis factor-alpha can stimulate proliferation of some ovarian cancers, the cytotoxic activity of tumor necrosis factor-alpha has been amplified ex vivo by inhibitors of protein synthesis. Similar heterogeneity exists with regard to interleukin-1 where stimulation or inhibition of cell proliferation has been observed. Tumor-infiltrating lymphocytes from ascites fluid contain cells capable of major histocompatibility complex-restricted and major histocompatibility complex-nonrestricted cytotoxicity. Tumor-infiltrating lymphocytes and interleukin-2 have been combined with cytotoxic chemotherapy to treat advanced or recurrent disease. Bispecific monoclonal antibodies that react both with T cells and ovarian tumor cells have produced tumor inhibition in human tumor xenografts. Immunotoxins that contain OVB3 and pseudomonas exotoxin have been evaluated in a phase I clinical trial. Dose-limiting central neurotoxicity has been observed without tumor regression. A monoclonal antibody designated OVX1 has been developed against a high-molecular-weight mucinlike molecule associated with ovarian cancers.(ABSTRACT TRUNCATED AT 250 WORDS)