This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Rowinsky, E. K. Articles by Ludwig, D. L. Search for Related Content PubMed PubMed Citation Articles by Rowinsky, E. K. Articles by Ludwig, D. L.

IMC-A12, a Human IgG₁ Monoclonal Antibody to the Insulin-Like Growth Factor I Receptor

Authors' Affiliations: ¹ Department of Clinical Research and Regulatory Affairs, ImClone Systems Incorporated, Branchburg, New Jersey and ² Department of Research, ImClone Systems Incorporated, New York, New York

Requests for reprints: Eric K. Rowinsky, ImClone Systems Incorporated, 33 ImClone Drive, Branchburg, NJ 08876. Phone: 908-203-6912; Fax: 908-231-9885; E-mail: eric.rowinsky{at}imclone.com.

Targeted monoclonal antibody therapy is an important strategy in cancer therapeutics. Among the most promising characteristics of therapeutic targets are those that modulate the growth and survival of malignant neoplasms and their sensitivity to anticancer therapies. The insulin-like growth factor-I receptor (IGF-IR) is overexpressed in many types of solid and hematopoietic malignancies, and has been implicated as a principal cause of heightened proliferative and survival signaling. IGF-IR has also been shown to confer resistance to cytotoxic, hormonal, and targeted therapies, suggesting that therapeutics targeting IGF-IR may be effective against a broad range of malignancies. IMC-A12 (ImClone Systems Incorporated), a fully human monoclonal IgG₁ antibody that binds with high affinity to the IGF-IR, inhibits ligand-dependent receptor activation and downstream signaling. IMC-A12 also mediates robust internalization and degradation of the IGF-IR. In human tumor xenograft models, IGF-IR blockade by IMC-A12 results in rapid and profound growth inhibition of cancers of the breast, lung, colon, and pancreas, and many other neoplasms. Although promising single-agent activity has been observed, the most impressive effects of targeting the IGF-IR with IMC-A12 have been noted when this agent was combined with cytotoxic agents or other targeted therapeutics. The results with IMC-A12 to date suggest that it may be an effective therapeutic in a diverse array of oncologic indications.