TY  - JOUR
A1  - Öhlschläger, Peter
A1  - Quetting, Michael
A1  - Alvarez, Gerardo
A1  - Dürst, Matthias
A1  - Gissmann, Lutz
A1  - Kaufmann, Andreas M.
T1  - Enhancement of immunogenicity of a therapeutic cervical cancer DNA-based vaccine by co-application of sequence-optimized genetic adjuvants
JF  - International Journal of Cancer
Y1  - 2009
SN  - 1097-0215
VL  - 125
IS  - 1
SP  - 189
EP  - 198
PB  - Wiley
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - Oosterhuis, Koen
A1  - Öhlschläger, Peter
A1  - Berg, Joost H. van den
A1  - Toebes, Mireille
A1  - Gomez, Raquel
A1  - Schumacher, Ton N.
A1  - Haanen, John B.
T1  - Preclinical development of highly effective and safe DNA vaccines directed against HPV 16 E6 and E7
JF  - International Journal of Cancer
Y1  - 2011
SN  - 1097-0215
VL  - 129
IS  - 2
SP  - 397
EP  - 406
PB  - Wiley
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - Öhlschläger, Peter
A1  - Spies, Elmar
A1  - Alvarez, Gerardo
A1  - Quetting, Michael
A1  - Groettrup, Marcus
T1  - The combination of TLR-9 adjuvantation and electroporation-mediated delivery enhances in vivo antitumor responses after vaccination with HPV-16 E7 encoding DNA
JF  - International Journal of Cancer. 128 (2011), H. 2
Y1  - 2011
SN  - 1097-0215
SP  - 473
EP  - 481
PB  - Wiley
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - Leurs, Ulrike
A1  - Mezo, Gabor
A1  - Öhlschläger, Peter
A1  - Orban, Erika
A1  - Marquard, Andrea
A1  - Manea, Marilena
T1  - Design, synthesis, in vitro stability and cytostatic effect of multifunctional anticancer drug-bioconjugates containing GnRH-III as a targeting moiety
JF  - Peptide Science
N2  - Bioconjugates containing the GnRH-III hormone decapeptide as a targeting moiety are able to deliver chemotherapeutic agents specifically to cancer cells expressing GnRH receptors, thereby increasing their local efficacy while limiting the peripheral toxicity. However, the number of GnRH receptors on cancer cells is limited and they desensitize under continuous hormone treatment. A possible approach to increase the receptor mediated tumor targeting and consequently the cytostatic effect of the bioconjugates would be the attachment of more than one chemotherapeutic agent to one GnRH-III molecule. Here we report on the design, synthesis and biochemical characterization of multifunctional bioconjugates containing GnRH-III as a targeting moiety and daunorubicin as a chemotherapeutic agent. Two different drug design approaches were pursued. The first one was based on the bifunctional [4Lys]-GnRH-III (Glp-His-Trp-Lys-His-Asp-Trp-Lys-Pro-Gly-NH2) containing two lysine residues in positions 4 and 8, whose ϵ-amino groups were used for the coupling of daunorubicin. In the second drug design, the native GnRH-III (Glp-His-Trp-Ser-His-Asp-Trp-Lys-Pro-Gly-NH2) was used as a scaffold; an additional lysine residue was coupled to the ϵ-amino group of 8Lys in order to generate two free amino groups available for conjugation of daunorubicin. The in vitro stability/degradation of all synthesized compounds was investigated in human serum, as well as in the presence of rat liver lysosomal homogenate. Their cellular uptake was determined on human breast cancer cells and the cytostatic effect was evaluated on human breast, colon and prostate cancer cell lines. Compared with a monofunctional compound, both drug design approaches resulted in multifunctional bioconjugates with increased cytostatic effect.
Y1  - 2012
U6  - http://dx.doi.org/10.1002/bip.21640
SN  - 1097-0282
VL  - 98
IS  - 1
SP  - 1
EP  - 10
PB  - Wiley
CY  - New York, NY
ER  -