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A Phase I Study of an Allogeneic Cell Vaccine (VACCIMEL) With GM-CSF in Melanoma Patients

Barrio, María M.*; de Motta, Patricia T.*; Kaplan, Julio; von Euw, Erika M.*; Bravo, Alicia I.; Chacón, Reinaldo D.; Mordoh, José* †

doi: 10.1097/01.cji.0000208258.79005.5f
Clinical Studies

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 μg (group 2), 300 μg (group 3), 400 μg (group 4), and 600 μg (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 μg GM-CSF to VACCIMEL is useful in increasing the immune response.

*Centro de Investigaciones Oncológicas—FUCA, Zabala 2836

Instituto Alexander Fleming, Cramer 1180, 1426 Buenos Aires

Hospital Eva Perón, San Martín, Provincia de Buenos Aires, Argentina

Supported by grants from the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), the Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT), the University of Buenos Aires, the Fundación Sales, the Fundación para la Investigación y Prevención del Cancer (FUCA), the Fundación Pedro F. Mosoteguy, and the Fundación María Calderón de la Barca, Argentina.

Reprints: José Mordoh, MD, PhD, Centro de Investigaciones Oncológicas—FUCA, 1426 Buenos Aires, Argentina (e-mail:

Received for publication July 19, 2005; accepted January 2, 2006

© 2006 Lippincott Williams & Wilkins, Inc.