CLINICAL UTILITY OF MONOCLONAL ANTIBODIES AND RECOMBINANT IMMUNOGLOBULIN FORMS

单抗及其重组 免疫球蛋白(Ig)形式正在被开发和表征为 在治疗和诊断应用中用于一系列 人类癌症。治疗应用包括使用单抗或 重组免疫球蛋白与放射性核素、药物或前药结合。 活体诊断应用包括使用放射性标记免疫球蛋白 伽马扫描或术中伽玛术中使用的表格 探测探头，即放射免疫引导手术(RARS)。单抗 已开发的主要针对两种肿瘤抗原起反应。 它们是：(A)癌胚抗原(CEA)，发现于 胃肠道癌、胰腺癌、乳腺癌和非小细胞肺癌， 和(B)TAG-72，它存在于以下大多数 癌症类型：胃肠道癌、胰腺癌、乳腺癌、卵巢癌、 子宫内膜、前列腺和非小细胞肺。第一个抗TAG-72 研制的单抗为B72.3。111In标记的B72.3是第一个也是仍然 只有单抗被FDA批准用于体内治疗癌症。它有 已被批准用于结直肠癌和结直肠癌的肿瘤成像 卵巢癌。一系列高亲和力的抗TAG-72抗体 现在已经开发出来了。这些产品的原型是单抗CC49。 合作的I期和II期临床试验，以确定 放射性标记小鼠CC49的治疗效果目前正在进行中 在乳腺癌、前列腺癌、胃肠癌和卵巢癌中， 不使用重组干扰素上调TAG-72 表情。现在已经观察到一些客观的临床反应。 在卵巢癌、乳腺癌和前列腺癌方案中使用CC49。一个 使用放射性标记CC49和钻机的第三阶段临床试验是 目前正在进行中，并正在展示这一过程的能力 在大约25%的胃肠道手术中确定隐匿性病变。 现在重点放在生物特征上。 重组免疫球蛋白形成。这些包括单链FV分子，CDR 移植了人性化的表格，删除了域名的Ig表格。研究是 正在进行定义代谢模式的实验模型， 这些药物的药代动力学特性和肿瘤靶向性 多种重组免疫球蛋白形式，以优化治疗效果和 将毒性和宿主免疫反应降至最低。

Monoclonal Antibodies (MAbs) and their consequent recombinant immunoglobulin (Ig) forms are being developed and characterized for use in both therapeutic and diagnostic applications for a range of human cancers. Therapeutic applications involve the use of MAbs or recombinant Ig forms conjugated to radionuclides, drugs or prodrugs. In vivo diagnostic applications involve the use of radiolabeled Ig forms for use in gamma scanning or intraoperatively with a gamma detecting probe, i.e., radioimmuno-guided surgery (RIGS). The MAbs developed are principally reactive against two pancarcinoma antigens. They are (a) carcinoembryonic antigen (CEA), which is found in gastrointestinal, pancreatic, breast, and non-small cell lung cancer, and (b) TAG-72, which is found on the majority of the following carcinoma types: gastrointestinal, pancreatic, breast, ovarian, endometrial, prostate, and non-small cell lung. The first anti-TAG-72 MAb developed was B72.3. 111In-labeled B72.3 is the first and still only MAb to be approved by the FDA for in vivo use in cancer. It has been approved for the oncologic imaging for both colorectal cancer and ovarian cancer. A series of higher affinity anti-TAG-72 antibodies have now been developed. The prototype of these is MAb CC49. Collaborative Phase I and Phase II clinical trials to determine the therapeutic efficacy of radiolabeled murine CC49 are currently ongoing in breast , prostate, gastrointestinal and ovarian cancers, with and without the use of recombinant interferon to upregulate TAG-72 expression. Some objective clinical responses have now been observed in ovarian, breast, and prostate cancer protocols employing CC49. A Phase III clinical trial employing radiolabeled CC49 and RIGS is currently underway and is demonstrating the ability of this procedure to define occult lesions in approximately 25 % of GI surgery. Emphasis is now being placed on the biological characterization of recombinant Ig forms. These include single-chain Fv molecules, CDR grafted humanized forms, and domain deleted Ig forms. Studies are ongoing in experimental models to define metabolic patterns, pharmacokinetic properties, and tumor targeting ability of these various recombinant Ig forms to optimize therapeutic efficacy and minimize toxicity and host immune responses.