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Treatment With Autologous Antigen-Presenting Cells Activated With the HER-2 –Based Antigen Lapuleucel-T: Results of a Phase I Study in Immunologic and Clinical Activity in HER-2–Overexpressing Breast Cancer

John W. Park, Michelle E. Melisko, Laura J. Esserman, Lori A. Jones, Jami Breen Wollan, Robert Sims

From the University of California, San Francisco, San Francisco, CA; and Dendreon Corporation, Seattle, WA

Address reprint requests to John W. Park, MD, UCSF Comprehensive Cancer Center, University of California, San Francisco, 1600 Divisadero St, Box 1710, San Francisco, CA 94115-1710; e-mail: jpark{at}cc.ucsf.edu

Purpose: Lapuleucel-T (APC8024), an autologous active cellular immunotherapy, was prepared from peripheral-blood mononuclear cells, including antigen-presenting cells, that were activated in vitro with recombinant fusion protein BA7072. This antigen construct consisted of sequences from intracellular and extracellular domains of human epidermal growth factor receptor 2 (HER-2) linked to granulocyte-macrophage colony-stimulating factor. We conducted a phase I study to evaluate the safety and immunologic activity of lapuleucel-T in patients with HER-2–overexpressing metastatic breast cancer.

Patients and Methods: Metastatic breast cancer patients whose tumors overexpressed or amplified HER-2 were eligible. Patients underwent leukapheresis and subsequent lapuleucel-T infusion 2 days later at weeks 0, 2, and 4. Patients who achieved a partial response (PR) or had stable disease (SD) lasting through week 48 were eligible for re-treatment using the same protocol and dose as their initial treatment. End points included safety, immunologic activity, and antitumor activity.

Results: Nineteen patients were enrolled; 18 patients received treatment. Therapy was well tolerated, with no grade 3 or 4 adverse events associated with the treatment. Significant cellular immune responses specific for the immunizing antigen and HER-2 sequences were induced after treatment, as measured by lymphocyte proliferation and interferon gamma enzyme-linked immunospot assay. One patient experienced a PR lasting 6 months. Three additional patients had SD lasting more than 1 year.

Conclusion: Autologous active cellular immunotherapy with lapuleucel-T was feasible, safe, and well tolerated. The treatment stimulated significant immune responses, which were enhanced after boost infusions. Lapuleucel-T therapy was associated with tumor response or extended disease stabilization in some patients and warrants further investigation.

Supported in part by Grant No. U54 CA90788 from the National Institutes of Health; and by Grants No. NCI P50-CA 58207, U54-CA90788, U01 CA111234-01, and the Lauder fund.

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