Serial killing of tumor cells by cytotoxic T cells redirected with a CD19‐/CD3‐bispecific single‐chain antibody construct
Open accessAbstract
Certain bispecific antibodies exhibit an extraordinary potency and efficacy for target cell lysis by eliciting a polyclonal T‐cell response. One example is a CD19‐/CD3‐bispecific single‐chain antibody construct (bscCD19xCD3), which at femtomolar concentrations can redirect cytotoxic T cells to eliminate human B lymphocytes, B lymphoma cell lines and patient‐derived malignant B cells. Here we have further explored the basis for this high potency. Using video‐assisted microscopy, bscCD19xCD3 was found to alter the motility and activity of T cells from a scanning to a killing mode. Individual T cells could eliminate multiple target cells within a 9 hr time period, resulting in nuclear fragmentation and membrane blebbing of target cells. Complete target cell elimination was observed within 24 hr at effector‐to‐target cell ratios as low as 1:5. Under optimal conditions, cell killing started within minutes after addition of bscCD19xCD3, suggesting that the rate of serial killing was mostly determined by T‐cell movement and target cell scanning and lysis. At all times, T cells remained highly motile, and no clusters of T and target cells were induced by the bispecific antibody. Bystanding target‐negative cells were not detectably affected. Repeated target cell lysis by bscCD19xCD3‐activated T cells increased the proportion of CD19/CD3 double‐positive T cells, which was most likely a consequence of transfer of CD19 from B to T cells during cytolytic synapse formation. To our knowledge, this is the first study showing that a bispecific antibody can sustain multiple rounds of target cell lysis by T cells. © 2005 Wiley‐Liss, Inc.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
T cells are abundant, efficiently proliferate upon activation, are capable of killing multiple times, and efficiently infiltrate tumors, but do not express Fcγ receptors.
“They are abundant, efficiently proliferate upon activation, capable of killing multiple times 16 and efficiently infiltrate tumors, but do not express Fcγ receptors.”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [16]
BiTEs mediate serial killing of many target cells.
“This suggests that BiTEs mediate serial killing of many target cells, and this was actually demonstrated using video assisted microscopy. 16”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [16]
BiTEs are capable of inducing efficient lysis at effector to target ratios as low as 1:10.
“Moreover, BiTEs are capable of inducing efficient lysis at effector to target ratios (E:T) as low as 1:10.”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [16]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The Immunological Synapse of CTL Contains a Secretory Domain and Membrane Bridges
Stinchcombe, J. C., Bossi, G., Booth, S., & Griffiths, G. M. (2001) · Immunity · doi:10.1016/s1074-7613(01)00234-5 · Cited by 817 · see citing works
TCR-Mediated Internalization of Peptide-MHC Complexes Acquired by T Cells
Huang, J.-F., Yang, Y. M., Sepulveda, H., Shi, W., Hwang, I., Peterson, P. A., Jackson, M. R., Sprent, J., & Cai, Z. (1999) · Science · doi:10.1126/science.286.5441.952 · Cited by 462 · see citing works
Löffler, A., Kufer, P., Lutterbüse, R., Zettl, F., Daniel, P. T., Schwenkenbecher, J. M., Riethmüller, G., Dörken, B., & Bargou, R. C. (2000) · Blood · doi:10.1182/blood.v95.6.2098 · Cited by 445 · see citing works
Self-citationHLA class I antigen downregulation in human cancers: T-cell immunotherapy revives an old story
Hicklin, D. J., Marincola, F. M., & Ferrone, S. (1999) · Molecular Medicine Today · doi:10.1016/s1357-4310(99)01451-3 · Cited by 374 · see citing works
Dreier, T., Lorenczewski, G., Brandl, C., Hoffmann, P., Syring, U., Hanakam, F., Kufer, P., Riethmüller, G., Bargou, R. C., & Baeuerle, P. A. (2002) · International Journal of Cancer · doi:10.1002/ijc.10557 · Cited by 348 · see citing works
Self-citationThe role of B7 co‐stimulation in activation and differentiation ofCD4+and CD8+T cells
Adam, A. J. M., Schweitzer, A., & Sharpe, A. H. (1998) · Immunological Reviews · doi:10.1111/j.1600-065x.1998.tb01242.x · Cited by 301 · see citing works
Down-Regulation of HLA Class I Antigen-Processing Molecules in Malignant Melanoma
Kageshita, T., Hirai, S., Ono, T., Hicklin, D. J., & Ferrone, S. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65321-7 · Cited by 249 · see citing works
Characterization of a leukemic cell line of the pre‐B phenotype
Hurwitz, R. L., Hozier, J. C., LeBien, T. W., Minowada, J., Gajl-Peczalska, K., Kubonishi, I., & Kersey, J. (1979) · International Journal of Cancer · doi:10.1002/ijc.2910230206 · Cited by 246 · see citing works
Dreier, T., Baeuerle, P. A., Fichtner, I., Grün, M., Schlereth, B., Lorenczewski, G., Kufer, P., Lutterbüse, R., Riethmüller, G., Gjorstrup, P., et al. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.8.4397 · Cited by 191 · see citing works
Self-citationJohnsen, A. K., Templeton, D. J., Sy, M. S., & Harding, C. V. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.8.4224 · Cited by 173 · see citing works
Bispecific antibodies in cancer therapy
Segal, D. M., Weiner, G. J., & Weiner, L. M. (1999) · Current Opinion in Immunology · doi:10.1016/s0952-7915(99)00015-1 · Cited by 161 · see citing works
A revival of bispecific antibodies
Kufer, P., Lutterbüse, R., & Baeuerle, P. A. (2004) · Trends in Biotechnology · doi:10.1016/j.tibtech.2004.03.006 · Cited by 157 · see citing works
Self-citationLöffler, A., Gruen, M., Wuchter, C., Schriever, F., Kufer, P., Dreier, T., Hanakam, F., Baeuerle, P. A., Bommert, K., Karawajew, L., et al. (2003) · Leukemia · doi:10.1038/sj.leu.2402890 · Cited by 150 · see citing works
Self-citationPrognostic relevance of immunophenotyping in 379 patients with acute myeloid leukemia
Chang, H., Salma, F., Yi, Q. L., Patterson, B. J., Brien, B., & Minden, M. D. (2003) · Leukemia Research · doi:10.1016/s0145-2126(03)00180-2 · Cited by 137 · see citing works
Selective MHC expression in tumours modulates adaptive and innate antitumour responses
Rees, R. C., & Mian, S. (1999) · Cancer Immunology Immunotherapy · doi:10.1007/s002620050589 · Cited by 80 · see citing works
Tumor Escape from Immune Response: Mechanisms and Targets of Activity
Gabrilovich, D. I., & Pisarev, V. M. (2003) · Current Drug Targets · doi:10.2174/1389450033490849 · Cited by 73 · see citing works
Kufer, P., Mack, M., Gruber, R., Lutterbüse, R., Zettl, F., & Riethmüller, G. (1997) · Cancer Immunology Immunotherapy · doi:10.1007/s002620050431 · Cited by 51 · see citing works
Bispecific antibodies for polyclonal T-cell engagement.
Baeuerle, P. A., Kufer, P., & Lutterbüse, R. (2003) · PubMed · Cited by 50 · see citing works
Self-citationMiyagi, T., Tatsumi, T., Takehara, T., Kanto, T., Kuzushita, N., Sugimoto, Y., Jinushi, M., Kasahara, A., Sasaki, Y., Hori, M., et al. (2002) · Journal of Gastroenterology and Hepatology · doi:10.1046/j.1440-1746.2003.02921.x · Cited by 42 · see citing works
Zhu, Z., Phillips, G. D. L., & Carter, P. M. (1995) · International Journal of Cancer · doi:10.1002/ijc.2910620315 · Cited by 42 · see citing works
Zhu, Z., & Carter, P. M. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.155.4.1903 · Cited by 37 · see citing works
Immunological inhibition of carcinogenesis
Spadaro, M., Lanzardo, S., Curcio, C., Forni, G., & Cavallo, F. (2004) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-003-0483-7 · Cited by 33 · see citing works
Wimberger, P., Xiang, W., Mayr, D. C., Diebold, J., Dreier, T., Baeuerle, P. A., & Kimmig, R. (2003) · International Journal of Cancer · doi:10.1002/ijc.11056 · Cited by 30 · see citing works
Self-citationHönemann, D., Kufer, P., Rimpler, M., Chatterjee, M., Friedl, S., Riecher, F., Bommert, K., Dörken, B., & Bargou, R. C. (2004) · Leukemia · doi:10.1038/sj.leu.2403264 · Cited by 11 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Spadaro M, Lanzardo S, Curcio C, Forni G, Cavallo F. Immunologi- cal inhibition of carcinogenesis. Cancer Immunol Immunother 2004; 53:204-16.
Cited by
Sorted by citations
Top 10 Challenges in Cancer Immunotherapy
Hegde, P. S., & Chen, D. S. (2020) · Immunity · doi:10.1016/j.immuni.2019.12.011 · Cited by 2,238 · see citing works
Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia
Kantarjian, H. M., Stein, A. S., Gökbuget, N., Fielding, A. K., Schuh, A. C., Ribera, J., Wei, A. H., Dombret, H., Foà, R., Bassan, R., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1609783 · Cited by 2,156 · see citing works
Engineered antibody fragments and the rise of single domains
Holliger, P., & Hudson, P. J. (2005) · Nature Biotechnology · doi:10.1038/nbt1142 · Cited by 1,928 · see citing works
Topp, M. S., Gökbuget, N., Stein, A. S., Zugmaier, G., O'Brien, S., Bargou, R. C., Dombret, H., Fielding, A. K., Heffner, L., Larson, R. A., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(14)71170-2 · Cited by 1,269 · see citing works
Self-citationTumor Regression in Cancer Patients by Very Low Doses of a T Cell–Engaging Antibody
Bargou, R., Leo, E., Zugmaier, G., Klinger, M., Goebeler, M., Knop, S., Noppeney, R., Viardot, A., Hess, G., Schuler, M., et al. (2008) · Science · doi:10.1126/science.1158545 · Cited by 1,078 · see citing works
Self-citationT cell-engaging therapies — BiTEs and beyond
Goebeler, M.-E., & Bargou, R. C. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0347-5 · Cited by 658 · see citing works
Self-citationvon Stackelberg, A., Locatelli, F., Zugmaier, G., Handgretinger, R., Trippett, T. M., Rizzari, C., Bader, P., O'Brien, M. M., Brethon, B., Bhojwani, D., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.67.3301 · Cited by 614 · see citing works
Kontermann, R. E., & Brinkmann, U. (2015) · Drug Discovery Today · doi:10.1016/j.drudis.2015.02.008 · Cited by 585 · see citing works
Klinger, M., Brandl, C., Zugmaier, G., Hijazi, Y., Bargou, R. C., Topp, M. S., Gökbuget, N., Neumann, S., Goebeler, M., Viardot, A., et al. (2012) · Blood · doi:10.1182/blood-2012-01-400515 · Cited by 471 · see citing works
Self-citationBispecific T‐cell engagers for cancer immunotherapy
Huehls, A. M., Coupet, T. A., & Sentman, C. L. (2014) · Immunology and Cell Biology · doi:10.1038/icb.2014.93 · Cited by 469 · see citing works
Goebeler, M.-E., Knop, S. T., Viardot, A., Kufer, P., Topp, M. S., Einsele, H., Noppeney, R., Heß, G., Kallert, S., Mackensen, A., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2014.59.1586 · Cited by 429 · see citing works
Self-citationViardot, A., Goebeler, M.-E., Heß, G., Neumann, S., Pfreundschuh, M. G., Adrian, N., Zettl, F., Libicher, M., Sayehli, C. M., Stieglmaier, J., et al. (2016) · Blood · doi:10.1182/blood-2015-06-651380 · Cited by 378 · see citing works
Self-citationBlinatumomab: A historical perspective
Nagorsen, D., Kufer, P., Baeuerle, P. A., & Bargou, R. C. (2012) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.07.013 · Cited by 356 · see citing works
Self-citationBispecific antibodies for cancer therapy: The light at the end of the tunnel?
Chames, P., & Baty, D. (2009) · mAbs · doi:10.4161/mabs.1.6.10015 · Cited by 336 · see citing works
Seimetz, D., Lindhofer, H., & Bokemeyer, C. (2010) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2010.03.001 · Cited by 284 · see citing works
BiTEs: bispecific antibody constructs with unique anti-tumor activity
Wolf, E., Hofmeister, R., Kufer, P., Schlereth, B., & Baeuerle, P. A. (2005) · Drug Discovery Today · doi:10.1016/s1359-6446(05)03554-3 · Cited by 260 · see citing works
Self-citationCD20-TCB with Obinutuzumab Pretreatment as Next-Generation Treatment of Hematologic Malignancies
Bacac, M., Colombetti, S., Herter, S., Sam, J., Perro, M., Chen, S., Bianchi, R., Richard, M., Schoenle, A., Nicolini, V., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-0455 · Cited by 250 · see citing works
Cytotoxic T cells are able to efficiently eliminate cancer cells by additive cytotoxicity
Weigelin, B., den Boer, A. T., Wagena, E., Broen, K., Dolstra, H., de Boer, R. J., Figdor, C. G., Textor, J. C., & Friedl, P. (2021) · Nature Communications · doi:10.1038/s41467-021-25282-3 · Cited by 239 · see citing works
Hipp, S., Tai, Y., Blanset, D. L., Deegen, P., Wahl, J., Thomas, O. S., Rattel, B., Adam, P. J., Anderson, K. C., & Friedrich, M. (2016) · Leukemia · doi:10.1038/leu.2016.388 · Cited by 234 · see citing works
Einsele, H., Borghaei, H., Orlowski, R. Z., Subklewe, M. S., Roboz, G. J., Zugmaier, G., Kufer, P., Iskander, K. S., & Kantarjian, H. M. (2020) · Cancer · doi:10.1002/cncr.32909 · Cited by 233 · see citing works
CARs versus BiTEs: A Comparison between T Cell–Redirection Strategies for Cancer Treatment
Slaney, C. Y., Wang, P., Darcy, P. K., & Kershaw, M. H. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0297 · Cited by 231 · see citing works
Brown, P. A., Inaba, H., Annesley, C., Beck, J. C., Colace, S. I., Dallas, M. H., DeSantes, K. B., Kelly, K. M., Kitko, C. L., Lacayo, N. J., et al. (2020) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2020.0001 · Cited by 220 · see citing works
Bispecific antibodies for the treatment of B-cell lymphoma: promises, unknowns, and opportunities
Falchi, L., Vardhana, S. A., & Salles, G. (2022) · Blood · doi:10.1182/blood.2021011994 · Cited by 212 · see citing works
Zhu, M., Wu, B. M., Brandl, C., Johnson, J., Wolf, A., Chow, A. T., & Doshi, S. (2016) · Clinical Pharmacokinetics · doi:10.1007/s40262-016-0405-4 · Cited by 210 · see citing works
Self-citationBispecific antibodies in cancer immunotherapy
Dahlén, E., Veitonmäki, N., & Norlén, P. (2018) · Therapeutic Advances in Vaccines and Immunotherapy · doi:10.1177/2515135518763280 · Cited by 209 · see citing works
Jiang, Z., Jiang, X., Chen, S., Lai, Y., Wei, X., Li, B., Lin, S., Wang, S., Wu, Q., Liang, Q., et al. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00690 · Cited by 207 · see citing works
Bluemel, C., Hausmann, S., Fluhr, P., Sriskandarajah, M., Stallcup, W. B., Baeuerle, P. A., & Kufer, P. (2010) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-010-0844-y · Cited by 205 · see citing works
Self-citationBispecific T cell engager therapy for refractory rheumatoid arthritis
Bucci, L., Hagen, M., Rothe, T., Raimondo, M. G., Fagni, F., Tur, C., Wirsching, A., Wacker, J., Wilhelm, A., Auger, J.-P., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-02964-1 · Cited by 191 · see citing works
Brischwein, K., Parr, L., Pflanz, S., Volkland, J., Lumsden, J., Klinger, M., Locher, M., Hammond, S. A., Kiener, P., Kufer, P., et al. (2007) · Journal of Immunotherapy · doi:10.1097/cji.0b013e318156750c · Cited by 187 · see citing works
Self-citationBispecific and multispecific antibodies in oncology: opportunities and challenges
Goebeler, M.-E., Stuhler, G., & Bargou, R. C. (2024) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-024-00905-y · Cited by 191 · see citing works
Self-citationMode of cytotoxic action of T cell-engaging BiTE antibody MT110
Haas, C., Krinner, E., Brischwein, K., Hoffmann, P., Lutterbüse, R., Schlereth, B., Kufer, P., & Baeuerle, P. A. (2009) · Immunobiology · doi:10.1016/j.imbio.2008.11.014 · Cited by 179 · see citing works
Self-citationBaxevanis, C. N., Perez, S. A., & Papamichail, M. (2009) · Critical Reviews in Clinical Laboratory Sciences · doi:10.1080/10408360902937809 · Cited by 177 · see citing works
Lineage Switch in MLL‐Rearranged Infant Leukemia Following CD19‐Directed Therapy
Rayes, A., McMasters, R. L., & O'Brien, M. M. (2016) · Pediatric Blood & Cancer · doi:10.1002/pbc.25953 · Cited by 170 · see citing works
Blinatumomab: a CD19/CD3 bispecific T cell engager (BiTE) with unique anti-tumor efficacy
Goebeler, M.-E., & Bargou, R. C. (2016) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.3109/10428194.2016.1161185 · Cited by 170 · see citing works
Self-citationBispecific Antibodies and Antibody–Drug Conjugates for Cancer Therapy: Technological Considerations
Shim, H. (2020) · Biomolecules · doi:10.3390/biom10030360 · Cited by 167 · see citing works
Bi-specific Aptamers Mediating Tumor Cell Lysis
Boltz, A., Piater, B., Toleikis, L., Guenther, R., Kolmar, H., & Hock, B. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.238261 · Cited by 164 · see citing works
Lutterbuese, R., Raum, T., Kischel, R., Hoffmann, P., Mangold, S., Rattel, B., Friedrich, M., Thomas, O., Lorenczewski, G., Rau, D., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000976107 · Cited by 166 · see citing works
Self-citationTherapeutic bispecific T-cell engager antibody targeting the intracellular oncoprotein WT1
Dao, T., Pankov, D., Scott, A., Korontsvit, T., Zakhaleva, V., Xu, Y., Xiang, J., Yan, S., Guerreiro, M., Veomett, N. J., et al. (2015) · Nature Biotechnology · doi:10.1038/nbt.3349 · Cited by 164 · see citing works
BiTE: Teaching antibodies to engage T-cells for cancer therapy.
Baeuerle, P. A., Kufer, P., & Bargou, R. C. (2009) · PubMed · Cited by 159 · see citing works
Self-citationCAR-T Cells Inflict Sequential Killing of Multiple Tumor Target Cells
Davenport, A. J., Jenkins, M. R., Cross, R. S., Yong, C. S. M., Prince, H. M., Ritchie, D. S., Trapani, J. A., Kershaw, M. H., Darcy, P. K., & Neeson, P. J. (2015) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-15-0048 · Cited by 157 · see citing works
Klinger, M., Benjamin, J., Kischel, R., Stienen, S., & Zugmaier, G. (2016) · Immunological Reviews · doi:10.1111/imr.12393 · Cited by 156 · see citing works
An anti-CD3/anti–CLL-1 bispecific antibody for the treatment of acute myeloid leukemia
Leong, S. R., Sukumaran, S., Hristopoulos, M. L., Tótpál, K., Stainton, S. L., Lu, E., Wong, A., Tam, L., Newman, R., Vuillemenot, B. R., et al. (2016) · Blood · doi:10.1182/blood-2016-08-735365 · Cited by 155 · see citing works
T cell engaging bispecific antibody (T-BsAb): From technology to therapeutics
Wu, Z., & Cheung, N. V. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.08.005 · Cited by 151 · see citing works
Recent advances of bispecific antibodies in solid tumors
Yu, S., Li, A., Liu, Q., Yuan, X., Xu, H., Jiao, D., Pestell, R. G., Han, X., & Wu, K. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0522-z · Cited by 151 · see citing works
Recombinant bispecific antibodies for cancer therapy
Kontermann, R. E. (2005) · Acta Pharmacologica Sinica · doi:10.1111/j.1745-7254.2005.00008.x · Cited by 142 · see citing works
Brandl, C., Haas, C., d’Argouges, S., Fisch, T., Kufer, P., Brischwein, K., Prang, N. S., Bargou, R. C., Suzich, J., Baeuerle, P. A., et al. (2007) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-007-0298-z · Cited by 136 · see citing works
Self-citationReusch, U., Duell, J., Ellwanger, K., Herbrecht, C., Knackmuss, S. H. J., Fucek, I., Eser, M., McAleese, F., Molkenthin, V., Gall, F. L., et al. (2015) · mAbs · doi:10.1080/19420862.2015.1029216 · Cited by 132 · see citing works
Portell, C. A., Wenzell, & Advani, A. S. (2013) · Clinical Pharmacology Advances and Applications · doi:10.2147/cpaa.s42689 · Cited by 125 · see citing works
Feldmann, A., Arndt, C., Bergmann, R., Loff, S., Cartellieri, M., Bachmann, D., Aliperta, R., Hetzenecker, M., Ludwig, F., Albert, S., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.15572 · Cited by 120 · see citing works
Herrera, L., Santos, S. D. M., Vesga, M. Á., Anguíta, J., Martín‐Ruiz, I., Carrascosa, T., Juan, M., & Eguizábal, C. (2019) · Scientific Reports · doi:10.1038/s41598-019-55239-y · Cited by 119 · see citing works
Bispecific T cell engager (BiTE®) antibody constructs can mediate bystander tumor cell killing
Ross, S. L., Sherman, M., McElroy, P. L., Lofgren, J. A., Moody, G. E., Baeuerle, P. A., Coxon, A., & Arvedson, T. (2017) · PLoS ONE · doi:10.1371/journal.pone.0183390 · Cited by 118 · see citing works
Self-citationHoffman, L. M., & Gore, L. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00063 · Cited by 116 · see citing works
Hipp, S., Voynov, V., Drobits, B., Giragossian, C., Trapani, F., Nixon, A. E., Scheer, J. M., & Adam, P. J. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-0926 · Cited by 109 · see citing works
Herrmann, M., Krupka, C., Deiser, K., Brauchle, B., Marcinek, A., Wagner, A. O., Rataj, F., Mocikat, R., Metzeler, K. H., Spiekermann, K., et al. (2018) · Blood · doi:10.1182/blood-2018-05-849802 · Cited by 108 · see citing works
Mølhøj, M., Crommer, S., Brischwein, K., Rau, D., Sriskandarajah, M., Hoffmann, P., Kufer, P., Hofmeister, R., & Baeuerle, P. A. (2006) · Molecular Immunology · doi:10.1016/j.molimm.2006.09.032 · Cited by 104 · see citing works
Self-citationTranslation and Clinical Development of Bispecific T‐cell Engaging Antibodies for Cancer Treatment
Yuraszeck, T. M., Kasichayanula, S., & Benjamin, J. (2017) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.651 · Cited by 100 · see citing works
Ligand-Targeted Delivery of Therapeutic siRNA
Ikeda, Y., & Taira, K. (2006) · Pharmaceutical Research · doi:10.1007/s11095-006-9001-x · Cited by 101 · see citing works
Sloan, D. D., Lam, C. K., Irrinki, A., Liu, L., Tsai, A., Pace, C. S., Kaur, J., Murry, J. P., Balakrishnan, M., Moore, P. A., et al. (2015) · PLoS Pathogens · doi:10.1371/journal.ppat.1005233 · Cited by 100 · see citing works
Feldmann, A., Arndt, C., Töpfer, K., Stamova, S., Krone, F., Cartellieri, M., Koristka, S., Michalk, I., Lindemann, D., Schmitz, M., et al. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1200341 · Cited by 99 · see citing works
Biology drives the discovery of bispecific antibodies as innovative therapeutics
Nie, S., Wang, Z., Moscoso‐Castro, M., D'Souza, P., Lei, C., Xu, J., & Gu, J. (2020) · Antibody Therapeutics · doi:10.1093/abt/tbaa003 · Cited by 95 · see citing works
Novel antibodies as anticancer agents
Zafir‐Lavie, I., Michaeli, Y., & Reiter, Y. (2007) · Oncogene · doi:10.1038/sj.onc.1210372 · Cited by 91 · see citing works
Amann, M., Brischwein, K., Lutterbuese, P., Parr, L., Petersen, L., Lorenczewski, G., Krinner, E., Bruckmeier, S., Lippold, S., Kischel, R., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-2182 · Cited by 90 · see citing works
Self-citationOberst, M. D., Fuhrmann, S. R., Mulgrew, K. A., Amann, M., Cheng, L., Lutterbuese, P., Richman, L. K., Coats, S., Baeuerle, P. A., & Hammond, S. A. (2014) · mAbs · doi:10.4161/19420862.2014.975660 · Cited by 89 · see citing works
Self-citationBispecific antibodies engage T cells for antitumor immunotherapy
Choi, B. D., Cai, M., Bigner, D. D., Mehta, A. I., Kuan, C.-T., & Sampson, J. H. (2011) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2011.572874 · Cited by 88 · see citing works
Targeting Solid Tumors with Bispecific T Cell Engager Immune Therapy
Arvedson, T., Bailis, J. M., Britten, C. D., Klinger, M., Nagorsen, D., Coxon, A., Egen, J. G., & Martin, F. (2021) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-070620-104325 · Cited by 86 · see citing works
Signal transduction therapy of cancer
Levitzki, A., & Klein, S. (2010) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2010.04.001 · Cited by 85 · see citing works
Herrmann, I., Baeuerle, P. A., Friedrich, M., Murr, A., Filusch, S., Rüttinger, D., Majdoub, M. W., Sharma, S., Kufer, P., Raum, T., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013474 · Cited by 85 · see citing works
Self-citationGD2-Targeted Immunotherapy and Radioimmunotherapy
Dobrenkov, K., & Cheung, N. V. (2014) · Seminars in Oncology · doi:10.1053/j.seminoncol.2014.07.003 · Cited by 85 · see citing works
Bispecific antibodies and CARs: generalized immunotherapeutics harnessing T cell redirection
Zhukovsky, E. A., Morse, R. J., & Maus, M. V. (2016) · Current Opinion in Immunology · doi:10.1016/j.coi.2016.02.006 · Cited by 85 · see citing works
Haddox, C. L., Mangaonkar, A. A., Chen, D., Shi, M., He, R., Oliveira, J. L., Litzow, M. R., Al‐Kali, A., Hogan, W. J., & Elliott, M. A. (2017) · Blood Cancer Journal · doi:10.1038/bcj.2017.89 · Cited by 85 · see citing works
Jabbour, E. J., Düll, J., Yilmaz, M. E., Khoury, J. D., Ravandi, F., Jain, N., Einsele, H., Garcia‐Manero, G., Konopleva, M. Y., Short, N. J., et al. (2017) · American Journal of Hematology · doi:10.1002/ajh.24987 · Cited by 84 · see citing works
A review of blinatumomab, a novel immunotherapy
Newman, M. J., & Benani, D. J. (2015) · Journal of Oncology Pharmacy Practice · doi:10.1177/1078155215618770 · Cited by 83 · see citing works
Blinatumomab induces autologous T-cell killing of chronic lymphocytic leukemia cells
Wong, R., Pepper, C. J., Brennan, P., Nagorsen, D., Man, S., & Fegan, C. (2013) · Haematologica · doi:10.3324/haematol.2012.082248 · Cited by 83 · see citing works
Tumor-Antigen–Binding Bispecific Antibodies for Cancer Treatment
Weidle, U. H., Kontermann, R. E., & Brinkmann, U. (2014) · Seminars in Oncology · doi:10.1053/j.seminoncol.2014.08.004 · Cited by 83 · see citing works
Bispecific antibody platforms for cancer immunotherapy
Lameris, R., de Bruin, R. C. G., Schneiders, F. L., Henegouwen, P. M. P. V. B. E., Verheul, H. M. W., de Gruijl, T. D., & van der Vliet, H. J. (2014) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2014.08.003 · Cited by 82 · see citing works
Hammond, S. A., Lutterbuese, R., Roff, S. R., Lutterbuese, P., Schlereth, B., Bruckheimer, E., Kinch, M. S., Coats, S., Baeuerle, P. A., Kufer, P., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2760 · Cited by 81 · see citing works
Self-citationGrabert, R. C., Cousens, L. P., Smith, J. A., Olson, S., Gall, J., Young, W. B., Davol, P. A., & Lum, L. G. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-2005 · Cited by 79 · see citing works
d’Argouges, S., Wissing, S., Brandl, C., Prang, N. S., Lutterbuese, R., Kozhich, A., Suzich, J., Locher, M., Kiener, P. A., Kufer, P., et al. (2008) · Leukemia Research · doi:10.1016/j.leukres.2008.08.025 · Cited by 79 · see citing works
Self-citationNägele, V., Kratzer, A., Zugmaier, G., Holland, C., Hijazi, Y., Topp, M. S., Gökbuget, N., Baeuerle, P. A., Kufer, P., Wolf, A., et al. (2017) · Experimental Hematology and Oncology · doi:10.1186/s40164-017-0074-5 · Cited by 78 · see citing works
Self-citationLutterbuese, R., Raum, T., Kischel, R., Lutterbuese, P., Schlereth, B., Schaller, E., Mangold, S., Rau, D., Meier, P., Kiener, P. A., et al. (2009) · Journal of Immunotherapy · doi:10.1097/cji.0b013e31819b7c70 · Cited by 77 · see citing works
Self-citationAdvances in bispecific biotherapeutics for the treatment of cancer
May, C., Sapra, P., & Gerber, H. (2012) · Biochemical Pharmacology · doi:10.1016/j.bcp.2012.07.011 · Cited by 77 · see citing works
Clinical Pharmacology and Translational Aspects of Bispecific Antibodies
Trivedi, A., Stienen, S., Zhu, M., Li, H., Yuraszeck, T., Gibbs, J., Heath, T., Loberg, R., & Kasichayanula, S. (2017) · Clinical and Translational Science · doi:10.1111/cts.12459 · Cited by 76 · see citing works
Design and engineering of bispecific antibodies: insights and practical considerations
Madsen, A. V., Pedersen, L. E., Kristensen, P. K., & Goletz, S. (2024) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2024.1352014 · Cited by 76 · see citing works
Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease
Chao, Z., Mei, Q., Yang, C., Luo, J., Liu, P., Peng, H., Guo, X., Yin, Z., Li, L., & Wang, Z. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02332-6 · Cited by 81 · see citing works
Osada, T., Hsu, D. S., Hammond, S. A., Hobeika, A. C., Devi, G. R., Clay, T. M., Lyerly, H. K., & Morse, M. A. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6605364 · Cited by 75 · see citing works
Bispecific Antibodies as a Development Platform for New Concepts and Treatment Strategies
Yang, F., Wen, W., & Qin, W. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms18010048 · Cited by 75 · see citing works
Solid Tumor Immunotherapy with T Cell Engager‐Armed Oncolytic Viruses
Scott, E. M., Duffy, M. R., Freedman, J. D., Fisher, K. D., & Seymour, L. W. (2017) · Macromolecular Bioscience · doi:10.1002/mabi.201700187 · Cited by 74 · see citing works
Hernández‐Hoyos, G., Sewell, T., Bader, R., Bannink, J. E., Chenault, R. A., Daugherty, M., Dasovich, M., Fang, H., Gottschalk, R. J., Kumer, J., et al. (2016) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-15-0242 · Cited by 72 · see citing works
Protein Engineering Strategies for Improved Pharmacokinetics
Rondon, A., Mahri, S., Morales-Yánez, F., Dumoulin, M., & Rita Vanbever, A. (2021) · Advanced Functional Materials · doi:10.1002/adfm.202101633 · Cited by 71 · see citing works
Lehmann, S., Perera, R., Grimm, H.-P., Sam, J., Colombetti, S., Fauti, T., Fahrni, L., Schaller, T. H., Freimoser–Grundschober, A., Zielonka, J., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-2622 · Cited by 71 · see citing works
T Cell–Activating Bispecific Antibodies in Cancer Therapy
Trabolsi, A., Arumov, A., & Schatz, J. H. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1900496 · Cited by 70 · see citing works
Aldoss, I. T., Bargou, R. C., Nagorsen, D., Friberg, G. R., Baeuerle, P. A., & Forman, S. J. (2016) · Leukemia · doi:10.1038/leu.2016.391 · Cited by 70 · see citing works
Self-citationB7H6-Specific Bispecific T Cell Engagers Lead to Tumor Elimination and Host Antitumor Immunity
Wu, M.-R., Zhang, T., Gacerez, A. T., Coupet, T. A., DeMars, L. R., & Sentman, C. L. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1402517 · Cited by 68 · see citing works
Xu, Y. Y., Hijazi, Y., Wolf, A., Wu, B. M., Sun, Y., & Zhu, M. (2015) · CPT Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.12003 · Cited by 68 · see citing works
An Anti-B Cell Maturation Antigen Bispecific Antibody for Multiple Myeloma
Ramadoss, N. S., Schulman, A. D., Choi, S., Rodgers, D. T., Kazane, S. A., Kim, C. H., Lawson, B. R., & Young, T. S. (2015) · Journal of the American Chemical Society · doi:10.1021/jacs.5b01876 · Cited by 68 · see citing works
Liu, X., Barrett, D. M., Jiang, S., Fang, C., Kalos, M. D., Grupp, S. A., June, C. H., & Zhao, Y. (2016) · Blood Cancer Journal · doi:10.1038/bcj.2016.38 · Cited by 68 · see citing works
Advances in adult acute lymphoblastic leukemia therapy
Aldoss, I. T., & Stein, A. S. (2017) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428194.2017.1354372 · Cited by 67 · see citing works
Queudeville, M., & Ebinger, M. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10122544 · Cited by 65 · see citing works
T cell-mediated additive cytotoxicity – death by multiple bullets
Weigelin, B., & Friedl, P. (2022) · Trends in cancer · doi:10.1016/j.trecan.2022.07.007 · Cited by 65 · see citing works
- Authors
- Hoffmann, P., Hofmeister, R., Brischwein, K., Brandl, C., Crommer, S., Bargou, R., Itin, C., Prang, N., & Baeuerle, P. A.
- Affiliations
- Humboldt-Universität zu Berlin (DE)
- Corresponding author
- Baeuerle, Patrick A.
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2005-02
- Volume
- 115
- Issue
- 1
- Pages
- 98-104
- ISSN
- 0020-7136 (ISSN-L)
- 1097-0215
- OpenAlex
- W2015956932
- Cited by
- 344
- References
- 24
- Citations by year
- 2026: 10 · 2025: 21 · 2024: 13 · 2023: 22 · 2022: 21 · 2021: 28 · 2020: 23 · 2019: 15 · 2018: 19 · 2017: 31 · 2016: 30 · 2015: 29 · 2014: 17 · 2013: 10 · 2012: 11
- FWCI
- 5.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- International Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Keywords
- single-chain antibody, cytotoxic T lymphocytes, T cell redirection, serial murder, T cell motility, T cell activation, B lymphoma, B cells, tumor cell lysis
- MeSH terms
- B-Lymphocytes, Cell Membrane, Cell Nucleus, Cytotoxicity, Immunologic, Dose-Response Relationship, Drug, Flow Cytometry, Humans, Immunoglobulin Fragments, Immunotherapy, Interleukin-2, Kinetics, Lymphocyte Activation, Neoplasms, T-Lymphocytes, T-Lymphocytes, Cytotoxic, Time Factors, CD3 Complex, Antibodies, Bispecific, Microscopy, Video, Antigens, CD19, Cell Line, Tumor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
