Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2009 Sep 15;15(18):5937-44.
doi: 10.1158/1078-0432.CCR-08-3282. Epub 2009 Sep 1.

A phase I trial of immunotherapy with lapuleucel-T (APC8024) in patients with refractory metastatic tumors that express HER-2/neu

Prema P Peethambaram  1 , Michelle E Melisko, Kristine J Rinn, Steven R Alberts, Nicole M Provost, Lori A Jones, Robert B Sims, Lisa R C Lin, Mark W Frohlich, John W Park
Affiliations
Clinical Trial

A phase I trial of immunotherapy with lapuleucel-T (APC8024) in patients with refractory metastatic tumors that express HER-2/neu

Prema P Peethambaram et al. Clin Cancer Res. .

Abstract

Purpose: This study aimed to evaluate the safety of, immune response induced by, and efficacy of treatment with lapuleucel-T (APC8024) in patients with HER-2/neu-expressing tumors. Lapuleucel-T is an investigational active immunotherapy product consisting of autologous peripheral blood mononuclear cells, including antigen presenting cells, which are cultured ex vivo with BA7072, a recombinant fusion antigen consisting of portions of the intracellular and extracellular regions of HER-2/neu linked to granulocyte-macrophage colony-stimulating factor.

Experimental design: Patients with metastatic breast, ovarian, or colorectal cancer whose tumors expressed HER-2 were eligible. Patients underwent leukapheresis in week 0 and received lapuleucel-T infusions in weeks 0, 2, and 4. Patients who achieved a partial response or had stable disease through week 48 were eligible for re-treatment using the same protocol and dose as their initial treatment.

Results: Eighteen patients were enrolled and treated. Patients showed an immune response to the immunizing antigen (BA7072) at week 8 compared with week 0 as measured by T lymphocyte proliferation and IFN-gamma enzyme-linked immunospot assay. Therapy was well tolerated. The majority (94.7%) of adverse events associated with treatment were grade 1 or 2. Two patients experienced stable disease lasting > 48 weeks.

Conclusions: Autologous active cellular immunotherapy with lapuleucel-T stimulated an immune response specific to the immunizing antigen and seemed to be well tolerated. Further clinical studies to assess the clinical benefit for patients with HER/2-neu-expressing breast, ovarian, and colorectal cancer are warranted.

PubMed Disclaimer

Conflict of interest statement

Disclosure of Potential Conflicts of Interest

The conduct of this trial was supported by Dendreon Corporation.

Figures

Figure 1
Figure 1
T cell proliferation data for (A) BA7072 and (B) HER500 at 10 µg/mL. Interferon gamma (IFN-γ;) enzyme-linked immunospot (ELISPOT) data for (C) BA7072 and (D) HER500 at 10 µg/mL. Data are shown for each sample. Median response for each time point is indicated by the line. Orange, purple, and green marks represent breast, colon, and ovarian cancer patients, respectively. P-values associated with the change at each week from baseline were calculated using the Wilcoxon signed rank test.
See this image and copyright information in PMC

References

    1. Hsu FJ, Benike C, Fagnoni F, et al. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat Med. 1996;2:52–58. - PubMed
    1. Murphy G, Tjoa B, Ragde H, Kenny G, Boynton A. Phase I clinical trial: T-cell therapy for prostate cancer using autologous dendritic cells pulsed with HLA-A0201-specific peptides from prostate-specific membrane antigen. Prostate. 1996;29:371–380. - PubMed
    1. Burch PA, Breen JK, Buckner JC, et al. Priming tissue-specific cellular immunity in a phase I trial of autologous dendritic cells for prostate cancer. Clin Cancer Res. 2000;6:2175–2182. - PubMed
    1. Small EJ, Fratesi P, Reese DM, et al. Immunotherapy of hormone-refractory prostate cancer with antigen-loaded dendritic cells. J Clin Oncol. 2000;18:3894–3903. - PubMed
    1. Nestle FO, Alijagic S, Gilliet M, et al. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med. 1998;4:328–332. - PubMed

Publication types

MeSH terms