CLINICAL UTILITY OF MONOCLONAL ANTIBODIES AND RECOMBINANT IMMUNOGLOBULIN FORMS

单克隆抗体（mab）及其重组

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.