Novel Immunodiagnostics and -therapeutics

Antigen-specific and potentially novel pharmaceutic agents are developed from immunized animals essentially via hybridoma technology and from human beings via EBV transformation. The resulting sequence information to the corresponding immunoglobulin genes is used to clone single stranded antibody fragments. To optimize the constructs, additional recombinant technologies are used to end up in tailor-made novel products. Biological efficiency is documented in established in vitro and in vivo test systems including molecular imaging. After having finished these analyses, the recombinant proteins are further modified into diagnostically or therapeutically applicable products. These research activities are perfectly matching with the ones of the Department for Experimental Medicine and Immunotherapy at the Institute for Applied Medical Engineering of the University Hospital Aachen.

Spin-off

 

The PharmedArtis GmbH in the Fraunhofer IME is engaged in the marketing of recombinant immunotherapeutics produced in bacteria, yeast and mammalian cells.

 

References

Tur M.K., Huhn M., Jost E., Thepen T., Brümmendorf H., Barth S. – In vivo efficacy of the recombinant anti-CD64 immunotoxin H22(scFv)-ETA’ in a human acute myeloid leukemia xenograft tumor model. Int. J. Cancer 129(5): 1277-1282 (2011)

Kampmeier F., Niesen J., Koers A., Ribbert M., Brecht A., Fischer R., Kießling F., Barth S.*, Thepen T.* – Rapid optical imaging of EGF-receptor expression with a single chain antibody SNAP-tag fusion protein. European Journal of Nuclear Medicine and Molecular Imaging 37(19): 1926-1934 (2010)

Ribbert T., Thepen T., Tur M.K., Fischer R., Huhn M., Barth S. – Recombinant, ETA’-based CD64 immunotoxins: Improved efficacy by increased valency, both in vitro as well as in vivo in a chronic cutaneous inflammation model in hC64-transgenic mice. Br. J. Dermatology 2: 279-286 (2010)

Joerissen H., Bektas N., Dahl E., Hartmann A., ten Haaf A., Di Fiore S., Kiefer H., Thess A., Barth S.*, Klockenbring T.* - Production and characterization of monoclonal antibodies against RAI3 and its expression in human breast cancer. BMC Cancer 9: 200 (2009)

Kampmeier F., Ribbert M., Nachreiner T., Demsky S., Beaufils F., Brecht A., Barth S. – Site-specific, covalent labeling of recombinant antibody fragments via fusion to an engineered version of 6-O-methylguanine DNA alkyltransferase. Bioconjug. Chem. 20(5): 1010-1015 (2009)

Ranft K., Thepen T., Fischer R., Barth S.*, Stöcker M.* - Recombinant bispecific single chain antibody fragments induce Fc-gamma receptor mediated elimination of CD30+ lymphoma cells. Cancer Lett. 282(2): 187-194 (2009)

Stahnke B., Thepen T., Stöcker M., Rosinke R., Jost E., Fischer R., Tur M.K., Barth S. – Granzyme B-H22(scFv), a human immunotoxin targeting CD64 in acute myeloid leukaemia of monocyte subtypes. Molecular Cancer Therapeutics 7(9): 2924-2932 (2008)

Tur M.K., Neef I., Jost E., Galm E., Jäger G., Stöcker M., Ribbert M., Osieka R., Barth S. – Targeted restoration of downregulated DAPK2 tumor suppressor activity induces apoptosis in Hodgkin lymphoma cells. J. Immunother. 32 (5): 431-441 (2009)

Wüllner U., Neef I., Eller A., Kleines M., Tur M.K., Barth S. – Disease-specific induction of apoptosis by rationally designed bivalent aptamer-siRNA transcripts silencing eukaryotic elongation factor 2. Curr. Cancer Drug Targets 8(7): 554-465 (2008)

Hetzel C., Bachran C., Fischer R., Fuchs H., Barth S.*, Stöcker M.* – Small cleavable adapters enhance the specific cytotoxicity of a humanized immunotoxin against CD64-positive acute myeloid leukemia cells. J. Immunother. 31(4): 370-376 (2008)

Nachreiner T., Kampmeier F., Thepen T., Fischer R., Barth S.*, Stöcker M.* – Depletion of autoreactive B-lymphocytes by a recombinant myelin oligodendrocyte glycoprotein-based immunotoxin. J. Neuroimmunology 195(1-2): 28-35 (2008)

Bruell D., Bruns C.J., Yezhelyev M., Huhn M., Müller J., Ischenko I., von der Decken V., Fischer R., Finnern R., Jauch K.W., Barth S. – Recombinant anti-EGFR immunotoxin 425(scFv)-ETA’ demonstrates strong anti-tumor effect against disseminated human pancreatic cancer in nude mice. Int. J. Molec. Med. 15(2): 305-313 (2005)

Stöcker M., Klockenbring T., Huhn M., Nachreiner T., Wicklein D., Petersen A., Bauer R., Goerlich R., Fischer R., Barth S. – Antigen-specific targeting and elimination of EBV-transformed B-cells by allergen-toxins. Journal of Allergy and Clinical Immunology 116(4): 910-915 (2005)

* joint senior authorship