INCREASE OF THE IMMUNOSTIMULATORY EFFECT OF DENDRITIC CELLS BY PULSING WITH CA 19-9 PROTEIN
Angela Märten,1 Björn Schöttker,1 Carsten Ziske,1 Silvia Weineck,1 Peter Buttgereit,1 Dieter Huhn,2 Tilman Sauerbruch,1 Ingo G.H. Schmidt-Wolf1
1Medizinische Klinik und Poliklinik I, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany, 2Abteilung für Innere Medizin und Poliklinik m. S. Hämatologie und Onkologie, Humboldt-Universität zu Berlin, Germany
Abstract:
Previously, we and others could show a relative resistance of solid tumor cells to immunologic effector cells in vitro. This resistance could be one reason for the clinical phenomenon of resistance of patients with colon carcinoma or other solid tumors to immunologic therapeutic approaches. Here, we tested dendritic cells (DC) pulsed with CA 19-9 protein for their immunostimulatory capacity of immunologic effector cells against cells derived from colon and pancreatic carcinoma. DC cultures co-expressed CMRF-44 and CD1a, markers typical of DC, in 31.5% +/- 5.3% after 13 days of culture. Co-culture of NK-like T lymphocytes with DC led to a significant increase in cytotoxic activity as measured with a LDH release assay. Cytotoxic activity could be further increased using DC pulsed with CA 19-9 protein. The effect of CA 19-9 on increasing the cytotoxic effect of NK-like T lymphocytes was dose-dependent. Similarly, co-cultivation of DC with NK-like T cells derived from patients with metastatic pancreatic cancer and elevated CA 19-9 serum levels led to a significant increase in cytotoxic activity. In conclusion, DC pulsed with CA 19-9 protein are able to increase the cytotoxic activity of immunologic effector cells against colon carcinoma and pancreatic cancer cells. DC pulsed with CA 19-9 protein may have a major impact on immunotherapeutic protocols for cancer patients.