Lidor Y, Bast R C
Department of Medicine, Duke University Medical Center, Durham, N.C.
Nat Immun Cell Growth Regul. 1988;7(4):193-215.
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.
单克隆抗体的发展使得几种卵巢肿瘤相关抗原得以鉴定,这些抗原可能成为体内血清疗法的靶点。除了针对生长因子受体的抗体外,未经修饰的单克隆试剂必须激活补体(C')成分或结合效应细胞以破坏肿瘤靶点。抗体依赖性细胞介导的细胞毒性(ADCC)对于在体内清除肿瘤细胞可能尤为重要。功能活性效应细胞的短缺会限制用异种抗血清或单克隆试剂进行血清疗法的疗效。使用免疫刺激剂如短小棒状杆菌可增加小鼠腹腔和卵巢癌患者腹腔内用于ADCC的效应细胞数量和活性。腹腔内血清疗法可使抗体与减瘤手术和细胞毒性化疗后残留的卵巢肿瘤细胞微小沉积物直接接触。将单克隆抗体与放射性核素、药物或毒素结合可能会提高血清疗法的效力并克服效应细胞短缺的问题。迄今为止的临床研究已对放射性核素结合物进行了成像和治疗评估。疾病体积较小的患者对治疗有反应。临床前模型表明药物和毒素结合物也可能具有活性。最近的研究表明不同免疫毒素之间存在协同相互作用。卵巢癌可能是评估与上皮肿瘤细胞反应的免疫结合物的一个有价值的临床模型。