Combination immunotherapy with prostatic acid phosphatase pulsed antigen-presenting cells (provenge) plus bevacizumab in patients with serologic progression of prostate cancer after definitive local therapy

Cancer. 2006 Jul 1;107(1):67-74. doi: 10.1002/cncr.21956.


Background: APC8015 (sipuleucel-T) is a cellular prostate cancer vaccine containing autologous antigen-presenting cells (APC) loaded with PA2024, a recombinant prostatic acid phosphatase/granulocyte-macrophage-colony-stimulating factor fusion protein, as the immunogen. Bevacizumab is a recombinant antibody against vascular endothelial growth factor, a proangiogenic protein with inhibitory effects on APC. A clinical trial was conducted to determine the prostate-specific antigen (PSA) and immunomodulatory effects of this combination immunotherapy.

Methods: Patients with androgen-dependent prostate cancer who had received prior definitive therapy with nonmetastatic, recurrent disease as manifested by a rising PSA of between 0.4 ng/mL and 6.0 ng/mL were enrolled. APC8015 was given intravenously(i.v.) on Weeks 0, 2, and 4. Bevacizumab was given at a dose of 10 mg/kg i.v. on Weeks 0, 2, 4, and every 2 weeks thereafter until toxicity or disease progression. PSA changes were recorded and the PSA doubling time (PSADT) was calculated. Immune response versus PA2024 was measured at baseline and after treatment by T-cell proliferation and interferon-gamma enzyme-linked immunospot (ELISPOT) assays.

Results: Twenty-two patients were treated. One patient achieved a > or =50% decrease in PSA. Nine patients exhibited some decrease in PSA from baseline, ranging from 6% to 72%, with the PSA of 3 patients decreasing at least 25%. The median pretreatment PSADT for the 20 evaluable patients was 6.9 months and the median posttreatment PSADT was 12.7 months (P = .01). All patients demonstrated induction of an immune response against PA2024.

Conclusions: The combination of APC8015 and bevacizumab induces an immune response and modulates PSA in patients with biochemically recurrent prostate cancer.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Phosphatase
  • Aged
  • Angiogenesis Inhibitors / therapeutic use
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antigen-Presenting Cells / drug effects
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / transplantation
  • Bevacizumab
  • Cancer Vaccines / therapeutic use
  • Combined Modality Therapy
  • Disease Progression
  • Humans
  • Immunotherapy*
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Prostate-Specific Antigen / blood*
  • Prostatic Neoplasms / therapy*
  • Protein Tyrosine Phosphatases / immunology*
  • Protein Tyrosine Phosphatases / pharmacology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • Tissue Extracts / therapeutic use*


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Cancer Vaccines
  • Tissue Extracts
  • Bevacizumab
  • sipuleucel-T
  • Acid Phosphatase
  • prostatic acid phosphatase
  • Protein Tyrosine Phosphatases
  • Prostate-Specific Antigen