Increase of the immunostimulatory effect of dendritic cells by pulsing with CA 19-9 protein.
Previously, a relative resistance of solid tumor cells to immunologic effector cells was shown 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. In this study, dendritic cells (DCs) pulsed with CA 19-9 protein were tested for their immunostimulatory capacity of immunologic effector cells against cells derived from colon and pancreatic carcinoma. Dendritic cell cultures coexpressed CMRF-44 and CD1a, markers typical of DCs, in 31.5% +/- 5.3% after 13 days of culture. Coculture of NK-like T lymphocytes with DCs led to a significant increase in cytotoxic activity, as measured using a lactate dehydrogenase release assay. Cytotoxic activity could be further increased using DCs 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, cocultivation of DCs 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, DCs pulsed with CA 19-9 protein can increase the cytotoxic activity of immunologic effector cells against colon carcinoma and pancreatic cancer cells. Dendritic cells pulsed with CA 19-9 protein may have an important effect on immunotherapeutic protocols for patients with cancer.
Medizinische Klinik und Poliklinik I, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany.
A
A
Märten
B
B
Schöttker
C
C
Ziske
S
S
Weineck
P
P
Buttgereit
D
D
Huhn
T
T
Sauerbruch
I G
IG
Schmidt-Wolf
D000943:Antigens, Differentiation / Q000032:analysis; D018395:CA-19-9 Antigen / Q000276:immunology*; D002277:Carcinoma / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000473:pathology; D014407:Tumor Cells, Cultured
D000943:Antigens, Differentiation; D018395:CA-19-9 Antigen