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15 results on '"Niesen, J."'

1. Identification of the thermo-physical properties of a stratified tissue. Adiabatic hypodermic wall

Author

Alosaimi, M, Lesnic, D, and Niesen, J

Subjects
Quantitative Biology::Tissues and Organs, Physics::Medical Physics
Abstract

Biological living tissues possess thermophysical properties that are difficult to measure directly and their estimation is very important in order to decide the appropriate treatment procedure (e.g. place of inoculation and appropriate amount of drug dosage) in case an abnormality is detected. In the present paper, we numerically investigate, for the first time, the determination of several thermo-physical blood-tissue properties of a one-dimensional, multi-layered biological skin tissue subjected to external heating. In contrast to the usual parabolic model that assumes infinitely fast propagation of the heat signal, in the present paper, the bio-heat transfer in such a biological body is mathematically modelled by a hyperbolic partial differential equation, which takes into account that the thermal wave speed is finite. On the skin surface a convective boundary condition holds taking into account the heat exchange with the environment, whilst on the most inner wall of the tissue an adiabatic boundary condition applies. Then, in this framework, the piecewise constant thermo-physical properties of interest given by the thermal conductivity, heat capacity and blood perfusion rate are accurately and stably reconstructed from non-intrusive temperature measurements on the inner and outer boundaries of the multi-layered tissue by minimizing a weighted nonlinear least-squares objective function.

Published
2021

2. Solving the Vlasov–Maxwell equations using Hamiltonian splitting

Author

Li, Y, He, Y, Sun, Y, Niesen, J, Qin, H, and Liu, J

Subjects
Mathematics::Symplectic Geometry
Abstract

In this paper, the numerical discretizations based on Hamiltonian splitting for solving the Vlasov–Maxwell system are constructed. We reformulate the Vlasov–Maxwell system in Morrison–Marsden–Weinstein Poisson bracket form. Then the Hamiltonian of this system is split into five parts, with which five corresponding Hamiltonian subsystems are obtained. The splitting method in time is derived by composing the solutions to these five subsystems. Combining the splitting method in time with the Fourier spectral method and finite volume method in space gives the full numerical discretizations which possess good conservation for the conserved quantities including energy, momentum, charge, etc. In numerical experiments, we simulate the Landau damping, Weibel instability and Bernstein wave to verify the numerical algorithms.

Published
2019

4. Efficient targeting of CD13 on cancer cells by the immunotoxin scFv13-ETA ' and the bispecific scFv [13xds16]

Author

Grieger, E., Gresch, G., Niesen, J., Woitok, M., Barth, S., Fischer, R., Fendel, R., Stein, C., and Publica

Abstract

Treatment of cancer using standard chemotherapy still offers a poor prognosis combined with severe side effects. Novel antibody-based therapies have been shown to overcome low efficiency and lack of selectivity by targeting cancer-associated antigens, such as aminopeptidase CD13. We isolated a high-affinity CD13-specific single-chain fragment variable (scFv13) from a phage display library of V-genes from mice immunized with soluble antigen. An immunotoxin comprising the scFv13 and a truncated version of the exotoxin A of Pseudomonas aeruginosa (ETA', scFv13-ETA') and a bispecific scFv targeting CD13 and CD16 simultaneously (bsscFv[13xds16]) was generated and investigated for their therapeutic potential. Both fusion proteins bound specifically to target cells with high affinity. Furthermore, scFv13-ETA' inhibited the proliferation of human cancer cell lines efficiently at low concentrations (IC50 values of 408 pM-7 nM) and induced apoptosis (40-85% of target cells). The bsscFv triggered dose-dependent antibody-dependent cell-mediated cytotoxicity, resulting in the lysis of up to 23.9% A2058 cells, 18.0% MDA-MB-468 cells and 19.1% HL-60 cells. The provided data demonstrate potent therapeutic activity of the scFv13-ETA' and the bsscFv[13xds16]. The CD13-specific scFv is therefore suitable for the direct and specific delivery of both cytotoxic agents and effector cells to cancer-derived cells, making it ideal for further therapeutic evaluation.

Published
2017

5. A novel fully-human cytolytic fusion protein based on granzyme B shows in vitro cytotoxicity and ex vivo binding to solid tumors overexpressing the epidermal growth factor receptor

Author

Niesen, J., Hehmann-Titt, G., Woitok, M., Fendel, R., Barth, S., Fischer, R., Stein, C., and Publica

Abstract

Human cytolytic fusion proteins (hCFPs) offer a promising immunotherapeutic approach for the treatment of solid tumors, avoiding the immunogenicity and undesirable side-effects caused by immunotoxins derived from plants or bacteria. The well-characterized human serine protease granzyme B has already been used as a therapeutic pro-apoptotic effector domain. We therefore developed a novel recombinant hCFP (GbR201K-scFv1711) consisting of an epidermal growth factor receptor-specific human antibody fragment and a granzyme B point mutant (R201K) that is insensitive to serpin B9 (PI9), a natural inhibitor of wild-type granzyme B that is often expressed in solid tumors. We found that GbR201K-scFv1711 selectively bound to epidermoid cancer and rhabdomyosarcoma cells and was rapidly internalized by them. Nanomolar concentrations of GbR201K-scFv1711 achieved the specific killing of epidermoid cancer cells by inducing apoptosis, and similar effects were observed in rhabdomyosarcoma cells when GbR201K-scFv1711 was combined with the endosomolytic substance chloroquine. The novel hCFP was stable in serum and bound to human rhabdomyosarcoma tissue ex vivo. These data confirm that GbR201K-scFv1711 is a promising therapeutic candidate suitable for further clinical investigation.

Published
2016

6. Novel EGFR-specific immunotoxins based on panitumumab and cetuximab show in vitro and ex vivo activity against different tumor entities

Author

Niesen, J., Stein, C., Brehm, H., Hehmann-Titt, G., Fendel, R., Melmer, G., Fischer, R., Barth, S., and Publica

Abstract

Purpose: The epidermal growth factor receptor (EGFR) is overexpressed in many solid tumors. EGFR-specific monoclonal antibodies (mAbs), such as cetuximab and panitumumab, have been approved for the treatment of colorectal and head and neck cancer. To increase tissue penetration, we constructed single-chain fragment variable (scFv) antibodies derived from these mAbs and evaluated their potential for targeted cancer therapy. The resulting scFv-based EGFR-specific immunotoxins (ITs) combine target specificity of the full-size mAb with the cell-killing activity of a toxic effector domain, a truncated version of Pseudomonas exotoxin A (ETA). Methods: The ITs and corresponding imaging probes were tested in vitro against four solid tumor entities (rhabdomyosarcoma, breast, prostate and pancreatic cancer). Specific binding and internalization of the ITs scFv2112-ETA (from cetuximab) and scFv1711-ETA (from panitumumab) were demonstrated by flow cytometry and for the scFv-SNAP-ta g imaging probes by live cell imaging. Cytotoxic potential of the ITs was analyzed in cell viability and apoptosis assays. Binding of the ITs was proofed ex vivo on rhabdomyosarcoma, prostate and breast cancer formalin-fixed paraffin-embedded biopsies. Results: Both novel ITs showed significant pro-apoptotic and anti-proliferative effects toward the target cells, achieving IC50 values of 4 pM (high EGFR expression) to 460 pM (moderate EGFR expression). Additionally, rapid internalization and specific in vitro and ex vivo binding on patient tissue were confirmed. Conclusions: These data demonstrate the potent therapeutic activity of two novel EGFR-specific ETA-based ITs. Both molecules are promising candidates for further development toward clinical use in the treatment of various solid tumors to supplement the existing therapeutic regimes.

Published
2015

7. The Fc-alpha receptor is a new target antigen for immunotherapy of myeloid leukemia

Author

Mladenov, R., Hristodorov, D., Cremer, C., Hein, L., Kreutzer, F., Stroisch, T., Niesen, J., Brehm, H., Blume, T., Brummendorf, T.H., Jost, E., Thepen, T., Fischer, R., Stockmeyer, B., Barth, S., Stein, C., and Publica

Abstract

Antibody-based immunotherapy of leukemia requires the targeting of specific antigens on the surface of blasts. The Fc gamma receptor (CD64) has been investigated in detail, and CD64-targeting immunotherapy has shown promising efficacy in the targeted ablation of acute myeloid leukemia (AML), acute myelomonocytic leukemia (AMML) and chronic myeloid leukemia cells (CML). Here we investigate for the first time the potential of Fc alpha RI (CD89) as a new target antigen expressed by different myeloid leukemic cell populations. For specific targeting and killing, we generated a recombinant fusion protein comprising an anti-human CD89 single-chain Fragment variable and the well-characterized truncated version of the potent Pseudomonas aeruginosa exotoxin A (ETA'). Our novel therapeutic approach achieved in vitro EC50 values in range 0.2-3 nM depending on the applied stimuli, that is, interferon gamma or tumor necrosis factor alpha. We also observed a dose-dependent apoptosis-mediated cytotoxicity, which resulted in the elimination of up to 90% of the target cells within 72 hr. These findings were also confirmed ex vivo using leukemic primary cells from peripheral blood samples of three previously untreated patients. We conclude that CD89-specific targeting of leukemia cell lines can be achieved in vitro and that the efficient elimination of leukemic primary cells supports the potential of CD89-ETA' as a potent, novel immunotherapeutic agent.

Published
2015

8. Targeted killing of rhabdomyosarcoma cells by a MAP-based human cytolytic fusion protein

Author

Brehm, H., Hristodorov, D., Pardo, A., Mladenov, R., Niesen, J., Fischer, R., Tur, M.K., Barth, S., and Publica

Abstract

The treatment of rhabdomyosarcoma (RMS) is challenging, and the prognosis remains especially poor for high-grade RMS with metastasis. The conventional treatment of RMS is based on multi-agent chemotherapy combined with resection and radiotherapy, which are often marked by low success rate. Alternative therapeutic options include the combination of standard treatments with immunotherapy. We generated a microtubule-associated protein (MAP)-based fully human cytolytic fusion protein (hCFP) targeting the fetal acetylcholine receptor, which is expressed on RMS cells. We were able to express and purify functional scFv35-MAP from Escherichia coli cells. Moreover, we found that scFv35-MAP is rapidly internalized by target cells after binding its receptor, and exhibits specific cytotoxicity toward FL-OH1 and RD cells in vitro. We also confirmed that scFv35-MAP induces apoptosis in FL-OH1 and RD cells. The in vivo potential of scFv35-MAP will need to be considered in further studies.

Published
2015

9. Search for new color-octet vector particle decaying to t(t)over-bar in p(p)over-bar collisions at root s=1.96 TeV RID G-1087-2011 RID E-4473-2011

Author

Aaltonen, T, Adelman, J, Gonzalez, Ba, Amerio, S, Amidei, D, Anastassov, A, Annovi, A, Antos, J, Apollinari, G, Apresyan, A, Arisawa, T, Artikov, A, Asaadi, J, Ashmanskas, W, Attal, A, Aurisano, A, Azfar, F, Badgett, W, Barbaro Galtieri, A, Barnes, Ve, Barnett, Ba, Barria, P, Bartos, P, Bauer, G, Beauchemin, Ph, Bedeschi, F, Beecher, D, Behari, S, Bellettini, G, Bellinger, J, Benjamin, D, Beretvas, A, Bhatti, A, Binkley, M, Bisello, D, Bizjak, I, Blair, Re, Blocker, C, Blumenfeld, B, Bocci, A, Bodek, A, Boisvert, V, Bortoletto, D, Boudreau, J, Boveia, A, Brau, B, Bridgeman, A, Brigliadori, L, Bromberg, C, Brubaker, E, Budagov, J, Budd, Hs, Buddy, S, Burkett, K, Busetto, G, Bussey, P, Buzatu, A, Byrum, Kl, Cabrera, S, Calancha, C, Camarda, S, Campanelli, M, Campbell, M, Canelli, F, Canepa, A, Carls, B, Carlsmith, D, Carosi, R, Carrillo, S, Carron, S, Casal, B, Casarsa, M, Castro, A, Catastini, P, Cauz, D, Cavaliere, V, Cavalli Sforza, M, Cerri, A, Cerrito, L, Chang, Sh, Chen, Yc, Chertok, M, Chiarelli, G, Chlachidze, G, Chlebana, F, Cho, K, Chokheli, D, Chou, Jp, Chung, K, Chung, Wh, Chung, Ys, Chwalek, T, Ciobanu, Ci, Ciocci, Ma, Clark, A, Clark, D, Compostella, G, Convery, Me, Conway, J, Corbo, M, Cordelli, M, Cox, Ca, Cox, Dj, Crescioli, F, Almenar, Cc, Cuevas, J, Culbertson, R, Cully, Jc, Dagenhart, D, Datta, M, Davies, T, de Barbaro, P, de Cecco, S, Deisher, A, de Lorenzo, G, Dell'Orso, Mauro, Deluca, C, Demortier, L, Deng, J, Deninno, M, D'Errico, M, Di Canto, A, di Giovanni GP, Di Ruzza, B, Dittmann, Jr, D'Onofrio, M, Donati, Simone, Dong, P, Dorigo, T, Dube, S, Ebina, K, Elagin, A, Erbacher, R, Errede, D, Errede, S, Ershaidat, N, Eusebi, R, Fang, Hc, Farrington, S, Fedorko, Wt, Feild, Rg, Feindt, M, Fernandez, Jp, Ferrazza, C, Field, R, Flanagan, G, Forrest, R, Frank, M, Franklin, M, Freeman, Jc, Furic, I, Gallinaro, M, Galyardt, J, Garberson, F, Garcia, Je, Garfinkel, Af, Garosi, P, Gerberich, H, Gerdes, D, Gessler, A, Giagu, S, Giakoumopoulou, V, Giannetti, P, Gibson, K, Gimmell, Jl, Ginsburg, Cm, Giokaris, N, Giordani, M, Giromini, P, Giunta, M, Giurgiu, G, Glagolev, V, Glenzinski, D, Gold, M, Goldschmidt, N, Golossanov, A, Gomez, G, Gomez Ceballos, G, Goncharov, M, Gonzalez, O, Gorelov, I, Goshaw, At, Goulianos, K, Gresele, A, Grinstein, S, Grosso Pilcher, C, Group, Rc, Grundler, U, da Costa JG, Gunay Unalan, Z, Haber, C, Hahn, Sr, Halkiadakis, E, Han, By, Han, Jy, Happacher, E, Nara, K, Hare, D, Hare, M, Harr, Rf, Hartz, M, Hatakeyama, K, Hays, C, Heck, M, Heinrich, J, Herndon, M, Heuser, J, Hewamanage, S, Hidas, D, Hill, Cs, Hirschbuehl, D, Hocker, A, Hou, S, Houlden, M, Hsu, Sc, Hughes, Re, Hurwitz, M, Husemann, U, Hussein, M, Huston, J, Incandela, J, Introzzi, G, Iori, M, Ivanov, A, James, E, Jang, D, Jayatilaka, B, Jeon, Ej, Jha, Mk, Jindariani, S, Johnson, W, Jones, M, Joo, Kk, Jun, Sy, June, Je, Junk, Tr, Kamon, T, Kar, D, Karchin, Pe, Kato, Y, Kephart, R, Ketchum, W, Keung, J, Khotilovich, V, Kilminster, B, Kim, Dh, Kim, Hs, Kim, Hw, Kim, Je, Kim, Mj, Kim, Sb, Kim, Sh, Kim, Yk, Kimura, N, Kirsch, L, Klimenko, S, Kondo, K, Kong, Dj, Konigsberg, J, Korytov, A, Kotwal, Av, Kreps, M, Kroll, J, Krop, D, Krumnack, N, Kruse, M, Krutelyov, V, Kuhr, T, Kulkarni, Np, Kurata, M, Kwang, S, Laasanen, At, Lami, S, Lammel, S, Lancaster, M, Lander, Rl, Lannon, K, Lath, A, Latino, G, Lazzizzera, I, Lecompte, T, Lee, E, Lee, Hs, Lee, Js, Lee, Sw, Leone, S, Lewis, Jd, Lin, Cj, Linacre, J, Lindgren, M, Lipeles, E, Lister, A, Litvintsev, Do, Liu, C, Liu, T, Lockyer, Ns, Loginov, A, Lovas, L, Lucchesi, D, Lueck, J, Lujan, P, Lukens, P, Lungu, G, Lys, J, Lysak, R, Macqueen, D, Madrak, R, Maeshima, K, Makhoul, K, Maksimovic, P, Malde, S, Malik, S, Manca, G, Manousakis Katsikakis, A, Margaroli, F, Marino, C, Marino, Cp, Martin, A, Martin, V, Martinez, M, Martinez Ballarin, R, Mastrandrea, P, Mathis, M, Mattson, Me, Mazzanti, P, Mcfarland, Ks, Mclntyre, P, Mcnuty, R, Mehta, A, Mehtala, P, Menzione, A, Mesropian, C, Miao, T, Mietlicki, D, Miladinovic, N, Miller, R, Mills, C, Milnik, M, Mitra, A, Mitselmakher, G, Miyake, H, Moed, S, Moggi, N, Mondragon, Mn, Moon, Cs, Moore, R, Morello, Mj, Morlock, J, Fernandez, Pm, Mulmenstadt, J, Mukherjee, A, Muller, T, Murat, P, Mussini, M, Nachtman, J, Nagai, Y, Naganoma, J, Nakamura, K, Nakano, I, Napier, A, Nett, J, Neu, C, Neubauer, Ms, Neubauer, S, Niesen, J, Nodulman, L, Norman, M, Norniella, O, Nurse, E, Oakes, L, Oh, Sh, Oh, Yd, Oksuzian, I, Okusawa, T, Orava, R, Osterberg, K, Griso, Sp, Pagliarone, C, Palencia, E, Papadimitriou, V, Papaikonomou, A, Paramanov, Aa, Parks, B, Pashapour, S, Patrick, J, Pauletta, G, Paulini, M, Paus, C, Peiffer, T, Pellett, De, Penzo, A, Phillips, Tj, Piacentino, G, Pianori, E, Pinera, L, Pitts, K, Plager, C, Pondrom, L, Potamianos, K, Poukhov, O, Prokoshin, F, Pronko, A, Ptohos, F, Pueschel, E, Punzi, Giovanni, Pursley, J, Rademacker, Tj, Rahaman, A, Ramakrishnan, V, Ranjan, N, Redondo, I, Renton, R, Renz, M, Rescigno, M, Richter, S, Rimondi, F, Ristori, L, Robson, A, Rodrigo, T, Rodriguez, T, Rogers, E, Rolli, S, Roser, R, Rossi, M, Rossin, R, Roy, P, Ruiz, A, Russ, J, Rusu, V, Rutherford, B, Saarikko, H, Safonov, A, Sakumoto, Wk, Santi, L, Sartori, L, Sato, K, Savoy Navarro, A, Schlabach, R, Schmidt, A, Schmidt, Ee, Schmidt, Ma, Schmidt, Mp, Schmitt, M, Schwarz, T, Scodellaro, L, Scribano, A, Scuri, F, Sedov, A, Seidel, S, Seiya, Y, Semenov, A, Sexton Kennedy, L, Sforza, F, Sfyrla, A, Shalhout, Sz, Shears, T, Shepard, Pf, Shimojima, M, Shiraishi, S, Shochet, M, Shon, Y, Shreyber, I, Simonenko, A, Sinervo, P, Sisakyan, A, Slaughter, Aj, Slaunwhite, J, Sliwa, K, Smith, Jr, Snider, Fd, Snihur, R, Soha, A, Somalwar, S, Sorin, V, Squillacioti, P, Stanitzki, M, Denis, Rs, Stelzer, B, Stelzer Chilton, O, Stentz, D, Strologas, J, Strycker, Gl, Suh, Js, Sukhanov, A, Suslov, I, Taffard, A, Takashima, R, Takeuchi, Y, Tanaka, R, Tang, J, Tecchio, M, Teng, Pk, Thom, J, Thome, J, Thompson, Ga, Thomson, E, Tipton, P, Ttito Guzman, P, Tkaczyk, S, Toback, D, Tokar, S, Tollefson, K, Tomura, T, Tonelli, D, Torre, S, Torretta, D, Totaro, P, Tourneur, S, Trovato, M, Tsai, Sy, Tu, Y, Turini, N, Ukegawa, F, Uozumi, S, van Remortel, N, Varganov, A, Vataga, E, Vazquez, F, Velev, G, Vellidis, C, Vidal, M, Vila, I, Vilar, R, Vogel, M, Volobouev, I, Volpi, G, Wagner, P, Wagner, Rg, Wagner, Rl, Wagner, W, Wagner Kuhr, J, Wakisaka, T, Wallny, R, Wang, Sm, Warburton, A, Waters, D, Weinberger, M, Weinelt, J, Wester, Wc, Whitehouse, B, Whiteson, D, Wicklund, Ab, Wicklund, E, Wilbur, S, Williams, G, Williams, Hh, Wilson, P, Winer, Bl, Wittich, P, Wolbers, S, Wolfe, C, Wolfe, H, Wright, T, Wu, X, Wurthwein, F, Yagil, A, Yamamoto, K, Yamaoka, J, Yang, Uk, Yang, Yc, Yao, Wm, Yeh, Gp, Yi, K, Yoh, J, Yorita, K, Yoshida, T, Yu, Gb, Yu, I, Yu, Ss, Yun, Jc, Zanetti, A, Zeng, Y, Zhang, X, Zheng, Y, Zucchelli Sng, X, Zucchelli Slli, S., Aaltonen, T, Adelman, J, Gonzalez, Ba, Amerio, S, Amidei, D, Anastassov, A, Annovi, A, Antos, J, Apollinari, G, Apresyan, A, Arisawa, T, Artikov, A, Asaadi, J, Ashmanskas, W, Attal, A, Aurisano, A, Azfar, F, Badgett, W, Barbaro Galtieri, A, Barnes, Ve, Barnett, Ba, Barria, P, Bartos, P, Bauer, G, Beauchemin, Ph, Bedeschi, F, Beecher, D, Behari, S, Bellettini, G, Bellinger, J, Benjamin, D, Beretvas, A, Bhatti, A, Binkley, M, Bisello, D, Bizjak, I, Blair, Re, Blocker, C, Blumenfeld, B, Bocci, A, Bodek, A, Boisvert, V, Bortoletto, D, Boudreau, J, Boveia, A, Brau, B, Bridgeman, A, Brigliadori, L, Bromberg, C, Brubaker, E, Budagov, J, Budd, H, Buddy, S, Burkett, K, Busetto, G, Bussey, P, Buzatu, A, Byrum, Kl, Cabrera, S, Calancha, C, Camarda, S, Campanelli, M, Campbell, M, Canelli, F, Canepa, A, Carls, B, Carlsmith, D, Carosi, R, Carrillo, S, Carron, S, Casal, B, Casarsa, M, Castro, A, Catastini, P, Cauz, D, Cavaliere, V, Cavalli Sforza, M, Cerri, A, Cerrito, L, Chang, Sh, Chen, Yc, Chertok, M, Chiarelli, G, Chlachidze, G, Chlebana, F, Cho, K, Chokheli, D, Chou, Jp, Chung, K, Chung, Wh, Chung, Y, Chwalek, T, Ciobanu, Ci, Ciocci, Ma, Clark, A, Clark, D, Compostella, G, Convery, Me, Conway, J, Corbo, M, Cordelli, M, Cox, Ca, Cox, Dj, Crescioli, F, Almenar, Cc, Cuevas, J, Culbertson, R, Cully, Jc, Dagenhart, D, Datta, M, Davies, T, de Barbaro, P, de Cecco, S, Deisher, A, de Lorenzo, G, Dell'Orso, M, Deluca, C, Demortier, L, Deng, J, Deninno, M, D'Errico, M, Di Canto, A, di Giovanni, Gp, Di Ruzza, B, Dittmann, Jr, D'Onofrio, M, Donati, S, Dong, P, Dorigo, T, Dube, S, Ebina, K, Elagin, A, Erbacher, R, Errede, D, Errede, S, Ershaidat, N, Eusebi, R, Fang, Hc, Farrington, S, Fedorko, Wt, Feild, Rg, Feindt, M, Fernandez, Jp, Ferrazza, C, Field, R, Flanagan, G, Forrest, R, Frank, M, Franklin, M, Freeman, Jc, Furic, I, Gallinaro, M, Galyardt, J, Garberson, F, Garcia, Je, Garfinkel, Af, Garosi, P, Gerberich, H, Gerdes, D, Gessler, A, Giagu, S, Giakoumopoulou, V, Giannetti, P, Gibson, K, Gimmell, Jl, Ginsburg, Cm, Giokaris, N, Giordani, M, Giromini, P, Giunta, M, Giurgiu, G, Glagolev, V, Glenzinski, D, Gold, M, Goldschmidt, N, Golossanov, A, Gomez, G, Gomez Ceballos, G, Goncharov, M, Gonzalez, O, Gorelov, I, Goshaw, At, Goulianos, K, Gresele, A, Grinstein, S, Grosso Pilcher, C, Group, Rc, Grundler, U, da Costa, Jg, Gunay Unalan, Z, Haber, C, Hahn, Sr, Halkiadakis, E, Han, By, Han, Jy, Happacher, E, Nara, K, Hare, D, Hare, M, Harr, Rf, Hartz, M, Hatakeyama, K, Hays, C, Heck, M, Heinrich, J, Herndon, M, Heuser, J, Hewamanage, S, Hidas, D, Hill, C, Hirschbuehl, D, Hocker, A, Hou, S, Houlden, M, Hsu, Sc, Hughes, Re, Hurwitz, M, Husemann, U, Hussein, M, Huston, J, Incandela, J, Introzzi, G, Iori, M, Ivanov, A, James, E, Jang, D, Jayatilaka, B, Jeon, Ej, Jha, Mk, Jindariani, S, Johnson, W, Jones, M, Joo, Kk, Jun, Sy, June, Je, Junk, Tr, Kamon, T, Kar, D, Karchin, Pe, Kato, Y, Kephart, R, Ketchum, W, Keung, J, Khotilovich, V, Kilminster, B, Kim, Dh, Kim, H, Kim, Hw, Kim, Je, Kim, Mj, Kim, Sb, Kim, Sh, Kim, Yk, Kimura, N, Kirsch, L, Klimenko, S, Kondo, K, Kong, Dj, Konigsberg, J, Korytov, A, Kotwal, Av, Kreps, M, Kroll, J, Krop, D, Krumnack, N, Kruse, M, Krutelyov, V, Kuhr, T, Kulkarni, Np, Kurata, M, Kwang, S, Laasanen, At, Lami, S, Lammel, S, Lancaster, M, Lander, Rl, Lannon, K, Lath, A, Latino, G, Lazzizzera, I, Lecompte, T, Lee, E, Lee, H, Lee, J, Lee, Sw, Leone, S, Lewis, Jd, Lin, Cj, Linacre, J, Lindgren, M, Lipeles, E, Lister, A, Litvintsev, Do, Liu, C, Liu, T, Lockyer, N, Loginov, A, Lovas, L, Lucchesi, D, Lueck, J, Lujan, P, Lukens, P, Lungu, G, Lys, J, Lysak, R, Macqueen, D, Madrak, R, Maeshima, K, Makhoul, K, Maksimovic, P, Malde, S, Malik, S, Manca, G, Manousakis Katsikakis, A, Margaroli, F, Marino, C, Marino, Cp, Martin, A, Martin, V, Martinez, M, Martinez Ballarin, R, Mastrandrea, P, Mathis, M, Mattson, Me, Mazzanti, P, Mcfarland, K, Mclntyre, P, Mcnuty, R, Mehta, A, Mehtala, P, Menzione, A, Mesropian, C, Miao, T, Mietlicki, D, Miladinovic, N, Miller, R, Mills, C, Milnik, M, Mitra, A, Mitselmakher, G, Miyake, H, Moed, S, Moggi, N, Mondragon, Mn, Moon, C, Moore, R, Morello, MICHAEL JOSEPH, Morlock, J, Fernandez, Pm, Mulmenstadt, J, Mukherjee, A, Muller, T, Murat, P, Mussini, M, Nachtman, J, Nagai, Y, Naganoma, J, Nakamura, K, Nakano, I, Napier, A, Nett, J, Neu, C, Neubauer, M, Neubauer, S, Niesen, J, Nodulman, L, Norman, M, Norniella, O, Nurse, E, Oakes, L, Oh, Sh, Oh, Yd, Oksuzian, I, Okusawa, T, Orava, R, Osterberg, K, Griso, Sp, Pagliarone, C, Palencia, E, Papadimitriou, V, Papaikonomou, A, Paramanov, Aa, Parks, B, Pashapour, S, Patrick, J, Pauletta, G, Paulini, M, Paus, C, Peiffer, T, Pellett, De, Penzo, A, Phillips, Tj, Piacentino, G, Pianori, E, Pinera, L, Pitts, K, Plager, C, Pondrom, L, Potamianos, K, Poukhov, O, Prokoshin, F, Pronko, A, Ptohos, F, Pueschel, E, Punzi, G, Pursley, J, Rademacker, Tj, Rahaman, A, Ramakrishnan, V, Ranjan, N, Redondo, I, Renton, R, Renz, M, Rescigno, M, Richter, S, Rimondi, F, Ristori, L, Robson, A, Rodrigo, T, Rodriguez, T, Rogers, E, Rolli, S, Roser, R, Rossi, M, Rossin, R, Roy, P, Ruiz, A, Russ, J, Rusu, V, Rutherford, B, Saarikko, H, Safonov, A, Sakumoto, Wk, Santi, L, Sartori, L, Sato, K, Savoy Navarro, A, Schlabach, R, Schmidt, A, Schmidt, Ee, Schmidt, Ma, Schmidt, Mp, Schmitt, M, Schwarz, T, Scodellaro, L, Scribano, A, Scuri, F, Sedov, A, Seidel, S, Seiya, Y, Semenov, A, Sexton Kennedy, L, Sforza, F, Sfyrla, A, Shalhout, Sz, Shears, T, Shepard, Pf, Shimojima, M, Shiraishi, S, Shochet, M, Shon, Y, Shreyber, I, Simonenko, A, Sinervo, P, Sisakyan, A, Slaughter, Aj, Slaunwhite, J, Sliwa, K, Smith, Jr, Snider, Fd, Snihur, R, Soha, A, Somalwar, S, Sorin, V, Squillacioti, P, Stanitzki, M, Denis, R, Stelzer, B, Stelzer Chilton, O, Stentz, D, Strologas, J, Strycker, Gl, Suh, J, Sukhanov, A, Suslov, I, Taffard, A, Takashima, R, Takeuchi, Y, Tanaka, R, Tang, J, Tecchio, M, Teng, Pk, Thom, J, Thome, J, Thompson, Ga, Thomson, E, Tipton, P, Ttito Guzman, P, Tkaczyk, S, Toback, D, Tokar, S, Tollefson, K, Tomura, T, Tonelli, D, Torre, S, Torretta, D, Totaro, P, Tourneur, S, Trovato, M, Tsai, Sy, Tu, Y, Turini, N, Ukegawa, F, Uozumi, S, van Remortel, N, Varganov, A, Vataga, E, Vazquez, F, Velev, G, Vellidis, C, Vidal, M, Vila, I, Vilar, R, Vogel, M, Volobouev, I, Volpi, G, Wagner, P, Wagner, Rg, Wagner, Rl, Wagner, W, Wagner Kuhr, J, Wakisaka, T, Wallny, R, Wang, Sm, Warburton, A, Waters, D, Weinberger, M, Weinelt, J, Wester, Wc, Whitehouse, B, Whiteson, D, Wicklund, Ab, Wicklund, E, Wilbur, S, Williams, G, Williams, Hh, Wilson, P, Winer, Bl, Wittich, P, Wolbers, S, Wolfe, C, Wolfe, H, Wright, T, Wu, X, Wurthwein, F, Yagil, A, Yamamoto, K, Yamaoka, J, Yang, Uk, Yang, Yc, Yao, Wm, Yeh, Gp, Yi, K, Yoh, J, Yorita, K, Yoshida, T, Yu, Gb, Yu, I, Yu, S, Yun, Jc, Zanetti, A, Zeng, Y, Zhang, X, Zheng, Y, and Zucchelli, S.

Subjects
High Energy Physics::Lattice, Nuclear Theory, High Energy Physics::Phenomenology, High Energy Physics::Experiment
Abstract

We present the result of a search for a massive color-octet vector particle, (e.g. a massive gluon) decaying to a pair of top quarks in proton-antiproton collisions with a center-of-mass energy of 1.96 TeV. This search is based on 1.9 fb(-1) of data collected using the CDF detector during Run II of the Tevatron at Fermilab. We study t (t) over bar events in the lepton + jets channel with at least one b-tagged jet. A massive gluon is characterized by its mass, decay width, and the strength of its coupling to quarks. These parameters are determined according to the observed invariant mass distribution of top quark pairs. We set limits on the massive gluon coupling strength for masses between 400 and 800 GeV/c(2) and width-to-mass ratios between 0.05 and 0.50. The coupling strength of the hypothetical massive gluon to quarks is consistent with zero within the explored parameter space. (C) 2010 Elsevier B.V. All rights reserved.

Published
2010

10. In vitro effects and ex vivo binding of an EGFR-specific immunotoxin on rhabdomyosarcoma cells

Author

Niesen, J., Brehm, H., Stein, C., Berges, N., Pardo, A., Fischer, R., Haaf, A. ten, Gattenlöhner, S., Tur, M.K., Barth, S., and Publica

Abstract

PURPOSE: Rhabdomyosarcoma (RMS) is a rare and aggressive soft tissue sarcoma with limited treatment options and a high failure rate during standard therapy. New therapeutic strategies based on targeted immunotherapy are therefore much in demand. The epidermal growth factor receptor (EGFR) has all the characteristics of an ideal target. It is overexpressed in up to 80 % of embryonal RMS and up to 50 % of alveolar RMS tumors. We therefore tested the activity of the EGFR-specific recombinant immunotoxin (IT) 425(scFv)-ETA' against EGFR(+) RMS cells in vitro and ex vivo. METHODS: We tested the specific binding and internalization behavior of 425(scFv)-ETA' in RMS cell lines in vitro by flow cytometry, compared to the corresponding imaging probe 425(scFv)-SNAP monitored by live cell imaging. The cytotoxic activity of 425(scFv)-ETA' was tested using cell viability and apoptosis assays. Specific binding of the IT was confirmed on formalin-fixed paraffin-embedded tissue samples from two RMS patients. RESULTS: We confirmed the specific binding of 425(scFv)-ETA' to RMS cells in vitro and ex vivo. Both the IT and the corresponding imaging probe were rapidly internalized. The IT killed EGFR(+) RMS cells in a dose-dependent manner, while showing no effect against control cells. It showed specific apoptotic activity against one selected RMS cell line. CONCLUSIONS: This is the first study showing the promising therapeutic potential of a recombinant, EGFR-targeting, ETA'-based IT on RMS cells. We confirmed the selective killing with IC50 values of up to 50 pM, and immunohistochemical staining confirmed the specific ex vivo binding to primary RMS material.

Published
2014

11. Rapid optical imaging of EGF receptor expression with a single-chain antibody SNAP-tag fusion protein

Author

Kampmeier, F., Niesen, J., Koers, A., Ribbert, M., Brecht, A., Fischer, R., Kießling, F., Barth, S., Thepen, T., and Publica

Abstract

The epidermal growth factor receptor (EGFR) is overexpressed in several types of cancer and its inhibition can effectively inhibit tumour progression. The purpose of this study was to design an EGFR-specific imaging probe that combines efficient tumour targeting with rapid systemic clearance to facilitate non-invasive assessment of EGFR expression. Genetic fusion of a single-chain antibody fragment with the SNAP-tag produced a 48-kDa antibody derivative that can be covalently and site-specifically labelled with substrates containing 0 (6)-benzylguanine. The EGFR-specific single-chain variable fragment (scFv) fusion protein 425(scFv)SNAP was labelled with the near infrared (NIR) dye BG-747, and its accumulation, specificity and kinetics were monitored using NIR fluorescence imaging in a subcutaneous pancreatic carcinoma xenograft model. The 425(scFv)SNAP fusion protein accumulates rapidly and specifically at the tumour site. Its small size allows efficient renal clearance and a high tumour to background ratio (TBR) of 33.2 +/- 6.3 (n = 4) 10 h after injection. Binding of the labelled antibody was efficiently competed with a 20-fold excess of unlabelled probe, resulting in an average TBR of 6 +/- 1.35 (n = 4), which is similar to that obtained with a non-tumour-specific probe (5.44 +/- 1.92, n = 4). When compared with a full-length antibody against EGFR (cetuximab), 425(scFv)SNAP-747 showed significantly higher TBRs and complete clearance 72 h post-injection. The 425(scFv)SNAP fusion protein combines rapid and specific targeting of EGFR-positive tumours with a versatile and robust labelling technique that facilitates the attachment of fluorophores for use in optical imaging. The same approach could be used to couple a chelating agent for use in nuclear imaging.

Published
2010

12. Search for new color-octet vector particle decaying to t(t)over-bar in p(p)over-bar collisions at root s=1.96 TeV

Author

Aaltonen, T., Adelman, J., Gonzalez, B. A., Amerio, S., Amidei, D., Anastassov, A., Annovi, A., Antos, J., Apollinari, G., Apresyan, A., Arisawa, T., Artikov, A., Asaadi, J., Ashmanskas, W., Attal, A., Aurisano, A., Azfar, F., Badgett, W., Barbaro Galtieri, A., Barnes, V. E., Barnett, B. A., Barria, P., Bartos, P., Bauer, G., Beauchemin, P. H., Bedeschi, F., Beecher, D., Behari, S., Bellettini, G., Bellinger, J., Benjamin, D., Beretvas, A., Bhatti, A., Binkley, M., Bisello, D., Bizjak, I., Blair, R. E., Blocker, C., Blumenfeld, B., Bocci, A., Bodek, A., Boisvert, V., Bortoletto, D., Boudreau, J., Boveia, A., Brau, B., Bridgeman, A., Brigliadori, L., Bromberg, C., Brubaker, E., Budagov, J., Budd, H. S., Buddy, S., Burkett, K., Busetto, G., Bussey, P., Buzatu, A., Byrum, K. L., Cabrera, S., Calancha, C., Camarda, S., Campanelli, M., Campbell, M., Canelli, F., Canepa, A., Carls, B., Carlsmith, D., Carosi, R., Carrillo, S., Carron, S., Casal, B., Casarsa, M., Castro, A., Catastini, P., Cauz, D., Cavaliere, V., Cavalli Sforza, M., Cerri, A., Cerrito, L., Chang, S. H., Chen, Y. C., Chertok, M., Chiarelli, G., Chlachidze, G., Chlebana, F., Cho, K., Chokheli, D., Chou, J. P., Chung, K., Chung, W. H., Chung, Y. S., Chwalek, T., Ciobanu, C. I., Ciocci, MARIA AGNESE, Clark, A., Clark, D., Compostella, G., Convery, M. E., Conway, J., Corbo, M., Cordelli, M., Cox, C. A., Cox, D. J., Crescioli, F., Almenar, C. C., Cuevas, J., Culbertson, R., Cully, J. C., Dagenhart, D., Datta, M., Davies, T., Barbaro, P. d., Cecco, S. d., Deisher, A., Lorenzo, G. d., Dell'Orso, M., Deluca, C., Demortier, L., Deng, J., Deninno, M., D'Errico, M., Canto, A. D., G. P., Di, Ruzza, B. D., Dittmann, J. R., D'Onofrio, M., Donati, S., Dong, P., Dorigo, T., Dube, S., Ebina, K., Elagin, A., Erbacher, R., Errede, D., Errede, S., Ershaidat, N., Eusebi, R., Fang, H. C., Farrington, S., Fedorko, W. T., Feild, R. G., Feindt, M., Fernandez, J. P., Ferrazza, C., Field, R., Flanagan, G., Forrest, R., Frank, M., Franklin, M., Freeman, J. C., Furic, I., Gallinaro, M., Galyardt, J., Garberson, F., Garcia, J. E., Garfinkel, A. F., Garosi, P., Gerberich, H., Gerdes, D., Gessler, A., Giagu, S., Giakoumopoulou, V., Giannetti, P., Gibson, K., Gimmell, J. L., Ginsburg, C. M., Giokaris, N., Giordani, M., Giromini, P., Giunta, M., Giurgiu, G., Glagolev, V., Glenzinski, D., Gold, M., Goldschmidt, N., Golossanov, A., Gomez, G., Gomez Ceballos, G., Goncharov, M., Gonzalez, O., Gorelov, I., Goshaw, A. T., Goulianos, K., Gresele, A., Grinstein, S., Grosso Pilcher, C., Group, R. C., Grundler, U., J. G., Da, Gunay Unalan, Z., Haber, C., Hahn, S. R., Halkiadakis, E., Han, B. Y., Han, J. Y., Happacher, E., Nara, K., Hare, D., Hare, M., Harr, R. F., Hartz, M., Hatakeyama, K., Hays, C., Heck, M., Heinrich, J., Herndon, M., Heuser, J., Hewamanage, S., Hidas, D., Hill, C. S., Hirschbuehl, D., Hocker, A., Hou, S., Houlden, M., Hsu, S. C., Hughes, R. E., Hurwitz, M., Husemann, U., Hussein, M., Huston, J., Incandela, J., Introzzi, G., Iori, M., Ivanov, A., James, E., Jang, D., Jayatilaka, B., Jeon, E. J., Jha, M. K., Jindariani, S., Johnson, W., Jones, M., Joo, K. K., Jun, S. Y., June, J. E., Junk, T. R., Kamon, T., Kar, D., Karchin, P. E., Kato, Y., Kephart, R., Ketchum, W., Keung, J., Khotilovich, V., Kilminster, B., Kim, D. H., Kim, H. S., Kim, H. W., Kim, J. E., Kim, M. J., Kim, S. B., Kim, S. H., Kim, Y. K., Kimura, N., Kirsch, L., Klimenko, S., Kondo, K., Kong, D. J., Konigsberg, J., Korytov, A., Kotwal, A. V., Kreps, M., Kroll, J., Krop, D., Krumnack, N., Kruse, M., Krutelyov, V., Kuhr, T., Kulkarni, N. P., Kurata, M., Kwang, S., Laasanen, A. T., Lami, S., Lammel, S., Lancaster, M., Lander, R. L., Lannon, K., Lath, A., Latino, G., Lazzizzera, I., Lecompte, T., Lee, E., Lee, H. S., Lee, J. S., Lee, S. W., Leone, S., Lewis, J. D., Lin, C. J., Linacre, J., Lindgren, M., Lipeles, E., Lister, A., Litvintsev, D. O., Liu, C., Liu, T., Lockyer, N. S., Loginov, A., Lovas, L., Lucchesi, D., Lueck, J., Lujan, P., Lukens, P., Lungu, G., Lys, J., Lysak, R., Macqueen, D., Madrak, R., Maeshima, K., Makhoul, K., Maksimovic, P., Malde, S., Malik, S., Manca, G., Manousakis Katsikakis, A., Margaroli, F., Marino, C., Marino, C. P., Martin, A., Martin, V., Martinez, M., Martinez Ballarin, R., Mastrandrea, P., Mathis, M., Mattson, M. E., Mazzanti, P., Mcfarland, K. S., Mclntyre, P., Mcnuty, R., Mehta, A., Mehtala, P., Menzione, A., Mesropian, C., Miao, T., Mietlicki, D., Miladinovic, N., Miller, R., Mills, C., Milnik, M., Mitra, A., Mitselmakher, G., Miyake, H., Moed, S., Moggi, N., Mondragon, M. N., Moon, C. S., Moore, R., Morello, M. J., Morlock, J., Fernandez, P. M., Mulmenstadt, J., Mukherjee, A., Muller, T., Murat, P., Mussini, M., Nachtman, J., Nagai, Y., Naganoma, J., Nakamura, K., Nakano, I., Napier, A., Nett, J., Neu, C., Neubauer, M. S., Neubauer, S., Niesen, J., Nodulman, L., Norman, M., Norniella, O., Nurse, E., Oakes, L., S. H., Oh, Y. D., Oh, Oksuzian, I., Okusawa, T., Orava, R., Osterberg, K., Griso, S. P., Pagliarone, C., Palencia, E., Papadimitriou, V., Papaikonomou, A., Paramanov, A. A., Parks, B., Pashapour, S., Patrick, J., Pauletta, G., Paulini, M., Paus, C., Peiffer, T., Pellett, D. E., Penzo, A., Phillips, T. J., Piacentino, G., Pianori, E., Pinera, L., Pitts, K., Plager, C., Pondrom, L., Potamianos, K., Poukhov, O., Prokoshin, F., Pronko, A., Ptohos, F., Pueschel, E., Punzi, G., Pursley, J., Rademacker, T. J., Rahaman, A., Ramakrishnan, V., Ranjan, N., Redondo, I., Renton, R., Renz, M., Rescigno, M., Richter, S., Rimondi, F., Ristori, L., Robson, A., Rodrigo, T., Rodriguez, T., Rogers, E., Rolli, S., Roser, R., Rossi, M., Rossin, R., Roy, P., Ruiz, A., Russ, J., Rusu, V., Rutherford, B., Saarikko, H., Safonov, A., Sakumoto, W. K., Santi, L., Sartori, L., Sato, K., Savoy Navarro, A., Schlabach, R., Schmidt, A., Schmidt, E. E., Schmidt, M. A., Schmidt, M. P., Schmitt, M., Schwarz, T., Scodellaro, L., Scribano, A., Scuri, F., Sedov, A., Seidel, S., Seiya, Y., Semenov, A., Sexton Kennedy, L., Sforza, F., Sfyrla, A., Shalhout, S. Z., Shears, T., Shepard, P. F., Shimojima, M., Shiraishi, S., Shochet, M., Shon, Y., Shreyber, I., Simonenko, A., Sinervo, P., Sisakyan, A., Slaughter, A. J., Slaunwhite, J., Sliwa, K., Smith, J. R., Snider, F. D., Snihur, R., Soha, A., Somalwar, S., Sorin, V., Squillacioti, P., Stanitzki, M., Denis, R. S., Stelzer, B., Stelzer Chilton, O., Stentz, D., Strologas, J., Strycker, G. L., Suh, J. S., Sukhanov, A., Suslov, I., Taffard, A., Takashima, R., Takeuchi, Y., Tanaka, R., Tang, J., Tecchio, M., Teng, P. K., Thom, J., Thome, J., Thompson, G. A., Thomson, E., Tipton, P., Ttito Guzman, P., Tkaczyk, S., Toback, D., Tokar, S., Tollefson, K., Tomura, T., Tonelli, D., Torre, S., Torretta, D., Totaro, P., Tourneur, S., Trovato, M., Tsai, S. Y., Tu, Y., Turini, N., Ukegawa, F., Uozumi, S., Remortel, N. v., Varganov, A., Vataga, E., Vazquez, F., Velev, G., Vellidis, C., Vidal, M., Vila, I., Vilar, R., Vogel, M., Volobouev, I., Volpi, G., Wagner, P., Wagner, R. G., Wagner, R. L., Wagner, W., Wagner Kuhr, J., Wakisaka, T., Wallny, R., Wang, S. M., Warburton, A., Waters, D., Weinberger, M., Weinelt, J., Wester, W. C., Whitehouse, B., Whiteson, D., Wicklund, A. B., Wicklund, E., Wilbur, S., Williams, G., Williams, H. H., Wilson, P., Winer, B. L., Wittich, P., Wolbers, S., Wolfe, C., Wolfe, H., Wright, T., Wu, X., Wurthwein, F., Yagil, A., Yamamoto, K., Yamaoka, J., Yang, U. K., Yang, Y. C., Yao, W. M., Yeh, G. P., Yi, K., Yoh, J., Yorita, K., Yoshida, T., G. B., Yu, Yu, I., S. S., Yu, Yun, J. C., Zanetti, A., Zeng, Y., Zhang, X., Zheng, Y., and Zucchelli, S.

Subjects
PHYSICS, massive gluon, top quark
Published
2010

13. Brief an [Franz Reiter]

Author

Niesen, J.

Abstract

von J. Niesen, Deutsch, Verzeichnung=Description=Inventaire Februar 2013 Rekatalogisierung nach Findbuch zum Nachlass, Original und Briefkatalog

Published
1832
Full Text
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14. The efficient elimination of solid tumor cells by EGFR-specific and HER2-specific scFv-SNAP fusion proteins conjugated to benzylguanine-modified auristatin F

Author

Woitok M, Klose D, Niesen J, Richter W, Abbas M, Stein C, Fendel R, Bialon M, Püttmann C, Fischer R, Stefan Barth, Kolberg K, and Publica

Abstract

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.

15. SNAP-tag technology: a useful tool to determine affinity constants and other functional parameters of novel antibody fragments

Author

Niesen J, Sack M, Seidel M, Fendel R, Stefan Barth, Fischer R, Stein C, and Publica

Abstract

Antibody derivatives, such as the single chain fragment variable (scFv), can be developed as diagnostic and therapeutic tools in cancer research, especially in the form of fusion proteins. Such derivatives are easier to produce and modify than monoclonal antibodies (mAbs) and achieve better tissue/tumor penetration. The genetic modification of scFvs is also much more straightforward than the challenging chemical modification of mAbs. Therefore, we constructed two scFvs derived from the approved monoclonal antibodies cetuximab (scFv2112) and panitumumab (scFv1711), both of which are specific for the epidermal growth factor receptor (EGFR), a well-characterized solid tumor antigen. Both scFvs were genetically fused to the SNAP-tag, an engineered version of the human DNA repair enzyme O6-alkylguanine DNA alkyltransferase that allows the covalent coupling of benzylguanine (BG)-modified substrates such as fluorescent dyes.

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