Originally published as JCO Early Release 10.1200/JCO.2008.17.8954 on October 6 2008

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Anti–Cytotoxic T-Lymphocyte Antigen-4 Antibody: The First in an Emerging Class of Immunomodulatory Antibodies for Cancer Treatment

Lawrence Fong, Eric J. Small

From the Department of Medicine, Division of Hematology/Oncology, University of California, San Francisco, CA

Corresponding author: Lawrence Fong, MD, University of California at San Francisco, San Francisco, CA 94143-0511; e-mail: lfong{at}medicine.ucsf.edu

Purpose To evaluate the emerging role of immunomodulatory antibodies in cancer treatment. Antibodies (ipilimumab and tremelimumab) targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4), an inhibitory molecule on T cells, represent the vanguard of these new drugs.

Design We performed a systematic review of the clinical studies examining the clinical activity of anti–CTLA-4 antibodies. We also review the potential mechanisms and toxicities associated with these treatments.

Results Clinical activity with anti–CTLA-4 monoclonal antibodies (mAbs) has paved the way for additional T-cell immunomodulatory monoclonal antibody (mAb) approaches for the treatment of cancer to be investigated. Because anti–CTLA-4 mAbs target the immune system and not the tumor, they may provide significant potential advantages over traditional antitumor mAbs, chemotherapies, and immunotherapies (ie, vaccines and cytokines). Other antibodies, such as CD137 agonists, CD40 agonists, and PD-1 antagonists, are currently in various stages of preclinical and clinical development.

Conclusion Available clinical data suggest that anti–CTLA-4 mAbs are very different from traditional mAbs, chemotherapies, and immunotherapies in terms of patterns of response, duration of response, and adverse event profile. Ongoing clinical studies aim to establish the efficacy and safety of anti–CTLA-4 mAbs as monotherapy or in combination with other drugs for the treatment of metastatic melanoma and a variety of other cancer types.

published online ahead of print at www.jco.org on October 6, 2008.

Manuscript preparation by Gardiner-Caldwell US supported by Bristol-Myers Squibb.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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