Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Recruitment of dendritic cells and enhanced antigen specific immunoreactivity in cancer patients treated with granulocyte-monocyte colony stimulating factor and interleukin 2: results from a phase I-II clinical trial

P Correale 1, G Campoccia 2, L Micheli 3, G Cusi 4, S Sestini 4, R Petrioli 1, D Pozzessere 1, S Marsili 1, G Fanetti 2, G Giorgi 3, G Francini 1

1 Div Medical Oncology,, 3 Dept Pharmacology "Giorgio Segre, ", 4 Dept Molecular Biology, Faculty of Medicine, University of Siena;, 2 Blood Bank, Policlinico "Le Scotte;" Sienna, Italy,

AIMS: Granulocyte-monocyte colony stimulating factor (GM-CSF) and interleukin-2 (IL-2) act synergistically in generating an antigen specific CTL-immune-response in vitro. A clinical trial was performed in cancer patients administering sc hrGM-CSF followed by sc hrIL-2. The goal of this study was the evaluation of the toxicity profile, biomodulatory potential and anti-tumor activity of this new schedule of treatment. METHOD Twenty-two patients, (8 renal cell-, 8 colo-rectal-, 1 prostate-, 1 pancreatic carcinoma, 2 soft tissue sarcoma, 1 NSLC, and 1 malignant melanoma) were enrolled. The median age was 69.2 years. All patients gave an informed consent. Patients received 150 micro-g/day of hrGM-CSF, sc for five days, followed by sc hrIL-2 for 10 days and then by 15 day rest. Thereafter, a second cycle was begun. After two cycles, if side effects were negligible (< grade 2 toxicity) hrIL-2 dose was increased. hrIL-2 daily dose was escalated, starting with 0.25 MIU, in consecutive cohorts of three patients every two cycles. RESULTS Bone pain and fever were the most common side effects. Two partial remissions, 8 stable disease, and 6 progressions were recorded. After treatment: hemocytometric cell counts revealed an increase in monocyte, lymphocyte, and eosinophil cell number; flow cytometry PBMC study revealed an increase in circulating DC (CD34+, CD11c+, HLA-I, ABC+, HLA-Dr+, CD80+, CD83+, CD86+) and CD4+/CD45Ro+/HLA-Dr+ lymphocytes; influenza antigen-specific proliferation assays demonstrated an enhanced immunoreactivity. CONCLUSION we report that hrGM-CSF and hrIL-2 combination is active and well tolerated. The biological activity of this protocol might support TAA specific anticancer immunotherapy by increasing APC activity and T cell immune-competence in cancer patients.

KEY WORDS: Cancer-immunotherapy, Dendritic-cells, Phase-I-II-clinical trial.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on immunotherapy.