Publications Search Results
Now showing 1 - 10 of 25
PublicationComparison of a mouse and a novel human scFv-SNAP-auristatin F drug conjugate with potent activity against EGFR-overexpressing human solid tumor cells( 2017)
;Woitok, M. ;Klose, D. ;Fiore, S. di ;Richter, W. ;Stein, C. ;Gresch, G. ;Grieger, E. ;Barth, S. ;Fischer, R. ;Kolberg, K.Niesen, J.Antibody-drug conjugates (ADCs) can deliver toxins to specific targets such as tumor cells. They have shown promise in preclinical/clinical development but feature stoichiometrically undefined chemical linkages, and those based on full-size antibodies achieve only limited tumor penetration. SNAP-tag technology can overcome these challenges by conjugating benzylguanine-modified toxins to single-chain fragment variables (scFvs) with 1:1 stoichiometry while preserving antigen binding. Two (human and mouse) scFv-SNAP fusion proteins recognizing the epidermal growth factor receptor (EGFR) were expressed in HEK 293T cells. The purified fusion proteins were conjugated to auristatin F (AURIF). Binding activity was confirmed by flow cytometry/immunohistochemistry, and cytotoxic activity was confirmed by cell viability/apoptosis and cell cycle arrest assays, and a novel microtubule dynamics disassembly assay was performed. Both ADCs bound specifically to their target cells in vitro and ex vivo, indicating that the binding activity of the scFv-SNAP fusions was unaffected by conjugation to AURIF. Cytotoxic assays confirmed that the ADCs induced apoptosis and cell cycle arrest at nanomolar concentrations and microtubule disassembly. The SNAP-tag technology provides a platform for the development of novel ADCs with defined conjugation sites and stoichiometry. We achieved the stable and efficient linkage of AURIF to human or murine scFvs using the SNAP-tag technology, offering a strategy to improve the development of personalized medicines.
PublicationThe efficient elimination of solid tumor cells by EGFR-specific and HER2-specific scFv-SNAP fusion proteins conjugated to benzylguanine-modified auristatin F( 2016)
;Woitok, M. ;Klose, D. ;Niesen, J. ;Richter, W. ;Abbas, M. ;Stein, C. ;Fendel, R. ;Bialon, M. ;Püttmann, C. ;Fischer, R. ;Barth, S.Kolberg, K.Antibody-drug conjugates (ADCs) combine the potency of cytotoxic drugs with the specificity of monoclonal antibodies (mAbs). Most ADCs are currently generated by the nonspecific conjugation of drugâlinker reagents to certain amino acid residues in mAbs, resulting in a heterogeneous product. To overcome this limitation and prepare ADCs with a defined stoichiometry, we use SNAP-tag technology as an alternative conjugation strategy. This allows the site-specific conjugation of O(6)-benzylguanine (BG)-modified small molecules to SNAP-tag fusion proteins. To demonstrate the suitability of this system for the preparation of novel recombinant ADCs, here we conjugated SNAP-tagged single chain antibody fragments (scFvs) to a BG-modified version of auristatin F (AURIF). We used two scFv-SNAP fusion proteins targeting members of the epidermal growth factor receptor (EGFR) family that are frequently overexpressed in breast cancer.
Publication2 MHz repetition rate, 200 ps pulse duration from a monolithic passively Q-switched microchip laser( 2010)
;Steinmetz, A. ;Nodop, D. ;Limpert, J. ;Hohmuth, R. ;Richter, W.Tünnermann, A.We report on a diode-pumped, monolithic and passively Q-switched microchip laser generating 200 ps pulses at a wavelength of 1064 nm with a repetition rate of up to 2 MHz. By varying the pump intensity we can change the repetition rate in the range from 100 kHz to 2 MHz and achieve pulse energies from 400 nJ to 130 nJ respectively, while still maintaining singe transversal and longitudinal mode operation. The microchip laser is based on Nd:YVO4 as the gain medium and a SESAM as the passive Q-switch. It is monolithically bonded with spin-on-glass as the bonding agent. The timing jitter was measured to be shorter than 40 ns for low and 2.5 ns for high repetition rates resulting in a relative timing jitter smaller than 1%. The output of this type of laser can be amplified easily to the range of few tens of watts using only one amplification stage based on a photonic crystal fiber. The combination of picoseconds pulses, high average power and high repetition rates makes this system very interesting for many applications like e.g. micromachining with high processing speed and nonlinear frequency conversion with high average power.
Publication2 MHz repetition rate, 200 ps pulse duration from a monolithic, passively Q-switched microchip laser( 2009)
;Steinmetz, A. ;Nodop, D. ;Limpert, J. ;Hohmuth, R. ;Richter, W.Tünnermann, A.We present a monolithic passively Q-switched microchip laser generating 200 ps pulses at a wavelength of 1064 nm with a repetition rate of up to 2 MHz. While maintaining transversal and longitudinal single-mode operation, the pulse energy can be changed from 130 nJ to 400 nJ by varying the pump conditions of the laser. To the best of our knowledge, the repetition rate of 2 MHz is by far the highest ever reported from such lasers operating in the sub-ns regime.
PublicationMicrolens coupled photoconductive switch( 2009)
;Matthäus, G. ;Hohmuth, R. ;Voitsch, M. ;Richter, W. ;Pradarutti, B. ;Riehemann, S. ;Notni, G. ;Nolte, S.Tünnermann, A.
PublicationLarge-area microlens emitters for powerful THz emission( 2009)
;Matthäus, G. ;Nolte, S. ;Hohmuth, R. ;Voitsch, M. ;Richter, W. ;Pradarutti, B. ;Riehemann, S. ;Notni, G.Tünnermann, A.A microlens coupled large-area emitter based on low-temperature grown GaAs is presented. A hexagonal microlens array directs the incident pump light into every second gap of a finger electrode structure. Consequently, an unidirectional photocurrent at high acceleration field strengths (50 kV/cm) is achieved, which generates constructively superposed THz emission. Using a Ti:Sapphire oscillator with a maximum average power of about 3 W at a repetition rate of 80 MHz, a net IR-to-THz conversion efficiency up to 1.3x10(-4) and a THz average power of 280 mu W is achieved.
PublicationMicrolens coupled interdigital photoconductive switch( 2008)
;Matthäus, G. ;Nolte, S. ;Hohmuth, R. ;Voitsch, M. ;Richter, W. ;Pradarutti, B. ;Riehemann, S. ;Notni, G.Tünnermann, A.A large-area terahertz emitter based on an interdigital finger electrode photoconductive switch on low-temperature grown GaAs attached to a hexagonal microlens array is demonstrated. The hexagonal arranged microlenses direct the incident IR excitation pulses into specified electrode gaps, resulting in constructive interference in the terahertz far field. Using a Ti:sapphire oscillator running at 80 MHz with 150 fs pulses, 6.5 mu m THz average power at 540 mW optical excitation is obtained. The maximum IR-to-terahertz conversion efficiency achieved is >= 1.35x10(-5).
PublicationMicro lens coupled large area photoconductive switch for powerful THz emission( 2008)
;Matthäus, G. ;Hohmuth, R. ;Voitsch, M. ;Richter, W. ;Riehemann, S. ;Notni, G. ;Nolte, S.Tünnermann, A.Powerful THz emission based on a finger electrode photoconductive switch attached to a micro lens array is presented. A hexagonal packed lens array directs the incident pump light into specified electrode gaps, yielding only constructive interference in the THz far-field. Using a Ti:Sapphire system operating at 80 MHz with 150 fs pulses and 3 W maximum optical excitation, 0.28 mW THz average power is obtained. The maximum IR-to-THz conversion efficiency is 1.3×10-4.
PublicationIntracavity terahertz generation inside a high-energy ultrafast soliton fiber laser( 2008)
;Matthäus, G. ;Ortac, B. ;Limpert, J. ;Nolte, S. ;Hohmuth, R. ;Voitsch, M. ;Richter, W. ;Pradarutti, B.Tünnermann, A.Intracavity terahertz emission inside a high-energy ultrafast Yb-doped fiber laser is presented. The terahertz radiation is generated by a transient photocurrent induced at the surface of a saturable InGaAs multiquantum well grown by molecular beam epitaxy on top of a semiconductor Bragg reflector. This device simultaneously works as the saturable absorber mirror for initiating and managing the passive mode locking required for the ultrashort pulse operation of the laser system. The maximum terahertz average power achieved is 4.2 mu W, which reveals a net conversion efficiency of 3.1x10(-5).
PublicationNew gluing technique rejuvenates abandoned lasers( 2007)
;Nodop, D. ;Limpert, J. ;Hohmuth, R. ;Richter, W. ;Guina, M.Tünnermann, A.