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Unconjugated Monoclonal Antibodies as Anticancer Agents

1991; Elsevier BV; Volume: 11; Issue: 2 Linguagem: Inglês

10.1016/s0889-8561(22)00323-x

1557-8607

Paul B. Chapman, David A. Scheinberg, Joseph J. Dimaggio, Alan N. Houghton,

Peptidase Inhibition and Analysis

By virtue of their specificity and ability to induce inflammation, moAb are attractive anticancer agents. The moAb must first target the tumor, and several factors, other than moAb affinity and specificity, can affect how well this happens. Once bound to the tumor, a specific inflammatory response can be induced, which may involve complement fixation or ADCC or both. Augmentation of this inflammatory response might be possible using various cytokines. Other strategies for interfering with tumor growth using moAb include targeting growth factors or growth factor receptors and inducing an anti-idiotype network. Several therapeutic trials have been performed using moAb in cancer patients. Generally, treatment is well tolerated, although most patients develop anti-immunoglobulin antibodies directed against the xenogeneic moAb. Antitumor responses have been observed, although these are usually partial responses that are short-lived. New approaches to moAb therapy will involve CDR-grafted hyper-humanized moAb in which the CDR of the rodent moAb are grafted into a human IgG backbone. Humanization should result in less of an anti-immunoglobulin host response. In addition, genetic engineering of the antigen-binding site and Fc regions will allow optimization of specificity, affinity, and effector functions.