A phase I study of an allogeneic cell vaccine (VACCIMEL) with GM-CSF in melanoma patients

J Immunother. 2006 Jul-Aug;29(4):444-54. doi: 10.1097/01.cji.0000208258.79005.5f.

Abstract

We investigated whether recombinant human granulocyte-monocyte-colony-stimulating factor (rhGM-CSF) increased the immunogenicity of VACCIMEL, a vaccine consisting of 3 irradiated allogeneic melanoma cell lines. A phase I clinical trial was performed on 20 melanoma patients in stages IIB (n=2), III (n=10), and IV (n=8), who were disease free after surgery (n=16) or had minimal disease (n=4). Cohorts of 4 patients were vaccinated 4 times with VACCIMEL and bacillus Calmette Guerin (BCG) as adjuvant. Besides, the patients received placebo (group 1) or GM-CSF: 150 microg (group 2), 300 microg (group 3), 400 microg (group 4), and 600 microg (group 5) per vaccine. The combination of VACCIMEL and GM-CSF had low toxicity. Only in group 5, grade 2 thoracic pain (3/4 patients) and abdominal cramps (2/4 patients) were observed. Delayed-type hypersensitivity increased after vaccination and it was highest in group 4. Phytohemagglutinin stimulation of peripheral blood lymphocytes was analyzed in 9 patients: 4/9 had normal stimulation; 3/9 had low basal stimulation, which recovered after vaccination; and 2/9 were not stimulated. Antimelanoma antibodies preexisted in 9/19 patients; in 3/19 patients, antibodies anti-33 kd, 90 kd, and 100 kd antigens were induced by vaccination. IgG2 but not IgG1 antibodies were detected. Anti-BCG antibodies, mostly IgG2, reached the highest post/prevaccination ratio in group 4. Median serum interleukin-12 was lower in progressing patients (61.6 pg/mL) than in those without evident disease (89 pg/mL). Thus, its low toxicity and the induction of a predominantly cellular immune response suggest that the addition of 300 to 400 microg GM-CSF to VACCIMEL is useful in increasing the immune response.

Publication types

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

MeSH terms

  • Abdominal Pain / chemically induced
  • Administration, Cutaneous
  • Adolescent
  • Adult
  • Aged
  • Antibodies, Neoplasm / immunology
  • BCG Vaccine / adverse effects
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / therapeutic use*
  • Fatigue / chemically induced
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Humans
  • Immunotherapy, Adoptive / methods
  • Interleukin-10 / blood
  • Interleukin-12 / blood
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / physiology
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Melanoma / prevention & control*
  • Middle Aged
  • Phytohemagglutinins / pharmacology
  • Recombinant Proteins

Substances

  • Antibodies, Neoplasm
  • BCG Vaccine
  • Cancer Vaccines
  • Phytohemagglutinins
  • Recombinant Proteins
  • Interleukin-10
  • Interleukin-12
  • Granulocyte-Macrophage Colony-Stimulating Factor