title: A phase I study of an allogeneic cell vaccine (VACCIMEL) with GM-CSF in melanoma patients.
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.
authors.affiliation: Centro de Investigaciones Oncológicas-FUCA, Zabala 2836, Provincia de Buenos Aires, Argentina.
authors.forename: María M
authors.initials: MM
authors.lastname: Barrio
authors.forename: Patricia T
authors.initials: PT
authors.lastname: de Motta
authors.forename: Julio
authors.initials: J
authors.lastname: Kaplan
authors.forename: Erika M
authors.initials: EM
authors.lastname: von Euw
authors.forename: Alicia I
authors.initials: AI
authors.lastname: Bravo
authors.forename: Reinaldo D
authors.initials: RD
authors.lastname: Chacón
authors.forename: José
authors.initials: J
authors.lastname: Mordoh
mesh_terms: D015746:Abdominal Pain / Q000139:chemically induced; D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D000368:Aged; D000912:Antibodies, Neoplasm / Q000276:immunology; D001500:BCG Vaccine / Q000009:adverse effects; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D011994:Recombinant Proteins
chemical_list: D000912:Antibodies, Neoplasm; D001500:BCG Vaccine; D019496:Cancer Vaccines; D010835:Phytohemagglutinins; D011994:Recombinant Proteins; D016753:Interleukin-10; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor