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Clinical Trials |
Department of Oncology, Radiology and Clinical Immunology, Section of Oncology, Uppsala University Hospital, SE-751 85 Uppsala, Sweden [G. J. U.]; Department of Oncology and Cancer Centre Karolinska, Karolinska Hospital, SE-171 76 Stockholm, Sweden [J-E. F., S. M., S. K., H. M., H. R.]; Laboratory of Hematology, Huddinge University Hospital, SE-141 86 Stockholm, Sweden [M. H.]; and Aventis Pasteur, Lyon, France 69280 [M. C. B., P. M.]
Purpose: Colorectal carcinoma cells express the tumor-associated antigen epithelial cellular adhesion molecule (Ep-CAM)/KSA. Passive immunotherapy with monoclonal antibodies using this antigen has shown promising results. Ep-CAM might also be a target for active specific immunotherapy. Expression of the tumor antigen in a viral vector may facilitate appropriate antigen presentation. The feasibility of an Ep-CAM/KSA-specific therapeutic vaccination was investigated in cancer patients.
Experimental Design: The full-length Ep-CAM gene was inserted into the avipox virus ALVAC (ALVAC-KSA). Twelve radically operated colorectal carcinoma patients without evidence of remaining macroscopic disease (stages I, II, and III) entered the study. The first 6 patients were immunized with three injections of ALVAC-KSA (107.09 CCID50 per immunization) alone in weeks 0, 3, and 6. The subsequent 6 patients received the same schedule of ALVAC-KSA together with the adjuvant cytokine granulocyte macrophage colony-stimulating factor (GM-CSF; 75 µg/day for 4 consecutive days).
Results: The adverse reactions to the vaccinations were mild except for local skin reactions. In the ALVAC-KSA group a weak T-cell response was induced in 2 of 6 patients. In the ALVAC-KSA/GM-CSF group a marked IFN-
response (enzyme-linked immunospot) was induced in 5 of 6 patients. The T-cell response appeared late, 1 month after the last immunization, with a peak at 4–5 months after immunization. No IgG antibodies against Ep-CAM were detected. Before vaccination the majority of patients had a type 1 T-cell response (IFN-) against the vector, which was noted in healthy donors as well. All of the patients developed high titers of IgG antibodies against the vector, and the T-cell response was vigorously boosted.
Conclusions: ALVAC-KSA, in combination with low dose local administration of GM-CSF may induce a strong, IFN- T-cell response (type 1). ALVAC-KSA seems to be an interesting candidate as a cancer vaccine for future clinical development.
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