Phase I study of tumor Ag-loaded IL-12 secreting semi-mature DC for the treatment of pediatric cancer

Cytotherapy. 2007;9(8):755-70. doi: 10.1080/14653240701589221. Epub 2007 Oct 4.

Abstract

Background: Cancer vaccines employing DC in their capacity as APC have been tolerated well and have shown some efficacy in clinical studies. IL-12, a cytokine critical for type 1 T-helper (Th1) lymphocyte and cytotoxic T-lymphocyte (CTL) differentiation, when released from a DC-based cancer vaccine, may support the generation of a cellular T-cell response.

Methods: We applied tumor cell lysate plus keyhole limpet hemocyanin (KLH)-loaded and 48-h lipopolysaccharide (LPS) plus IFN-gamma-stimulated fully mature DC, which do not release IL-12, subcutaneously to eight patients, and maximally 6-h stimulated semi-mature (sm) DC, which are potent producers of IL-12, subcutaneously (n=6) or intranodally (n=8) as a cancer vaccine to patients suffering from advanced solid pediatric malignancies.

Results: No serious adverse events were observed following application of IL-12-releasing smDC. Following immunization the majority of patients responded positively to KLH in a delayed-type hypersensitivity (DTH) test. In addition, three of six intranodally treated patients responded to the tumor Ag in the DTH test.

Discussion: We conclude that treatment with a DC-based cancer vaccine enabled to release the immune regulatory cytokine IL-12 is safe and feasible and has the potential to induce a cellular immune response in pediatric cancer patients.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Antigen Presentation
  • Antigens, Neoplasm / immunology*
  • Cancer Vaccines* / immunology
  • Cancer Vaccines* / therapeutic use
  • Cell Differentiation
  • Child
  • Dendritic Cells / immunology*
  • Dendritic Cells / transplantation
  • Female
  • Hemocyanins / immunology
  • Humans
  • Immunotherapy, Adoptive
  • Injections, Intralymphatic
  • Injections, Subcutaneous
  • Interferon-gamma / immunology
  • Interleukin-12 / immunology
  • Interleukin-12 / metabolism
  • Lipopolysaccharides / immunology
  • Lymphocyte Activation
  • Male
  • Neoplasms / immunology*
  • Neoplasms / mortality
  • Neoplasms / therapy*
  • Treatment Outcome
  • Vaccination*

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Lipopolysaccharides
  • Interleukin-12
  • Interferon-gamma
  • Hemocyanins
  • keyhole-limpet hemocyanin