A recombinant bispecific single‐chain antibody induces targeted, supra‐agonistic CD28‐stimulation and tumor cell killing
Open accessAbstract
Endowing tumor cells with costimulatory signals for T cell activation has emerged as a promising strategy for tumor immunotherapy. Costimulatory molecules were either transfected into tumor cells to generate vaccines or were fused, e.g. to antibodies against tumor‐associated antigens, to achieve targeted T cell costimulation in vivo. Here we report the production and purification of rM28, a recombinant bispecific single‐chain antibody directed to a melanoma‐associated proteoglycan and to the costimulatory CD28 molecule on human T cells. We found that a dimer of the recombinant molecule, bound to tumor target cells, induced pronounced T cell activation in peripheral blood mononuclear cell preparations without additional TCR/CD3 stimulation being required. Thelytic activity generated after 3 days of stimulation effectively prevented tumor cell growth. However, it was unspecific and predominantly mediated by non T cells. Our findings demonstrate that presentation of a CD28 antibody within a suitable recombinant, bispecific format may result in a "targeted supra‐agonistic stimulation" of the CD28 molecule, which leads to effective tumor cell killing after induction of unspecifically lytic cells.
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?
rM28 spontaneously forms stable dimers and can induce T-cell activation and effective tumor-cell killing in vitro and in vivo without a signal through the TCR/CD3 complex.
“This molecule spontaneously forms stable dimers, and was shown to be capable of inducing T-cell activation and effective tumor-cell killing in vitro and in vivo without a signal through the TCR/CD3 complex, a so called”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [40]
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
CD28/B7 SYSTEM OF T CELL COSTIMULATION
Lenschow, D. J., Walunas, T. L., & Bluestone, J. A. (1996) · Annual Review of Immunology · doi:10.1146/annurev.immunol.14.1.233 · Cited by 2,717 · see citing works
CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation.
Krummel, M. F., & Allison, J. P. (1995) · The Journal of experimental medicine · doi:10.1084/jem.182.2.459 · Cited by 2,245 · see citing works
"Diabodies": small bivalent and bispecific antibody fragments.
Holliger, P., Prospero, T. D., & Winter, G. P. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.14.6444 · Cited by 879 · 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
Bispecific tandem diabody for tumor therapy with improved antigen binding and pharmacokinetics
Kipriyanov, S. M., Moldenhauer, G., Schuhmacher, J., Cochlovius, B., von der Lieth, C., Matys, E., & Little, M. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.3156 · Cited by 202 · see citing works
Levitsky, H. I., Montgomery, J. M., Ahmadzadeh, M., Staveley-O’Carroll, K. F., Guarnieri, F., Longo, D. L., & Kwak, L. W. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.156.10.3858 · Cited by 174 · see citing works
Protein L: An Immunoglobulin Light Chain-binding Bacterial Protein
Åkerström, B., & Björck, L. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)47174-3 · Cited by 158 · see citing works
Of mice and men: hybridoma and recombinant antibodies
Little, M., Kipriyanov, S. M., Gall, F. L., & Moldenhauer, G. (2000) · Immunology Today · doi:10.1016/s0167-5699(00)01668-6 · Cited by 157 · see citing works
Cure of Xenografted Human Tumors by Bispecific Monoclonal Antibodies and Human T Cells
Renner, C., Jung, W. E., Şahin, U., Denfeld, R. W., Pohl, C., Trümper, L. H. P., Hartmann, F., Diehl, V., van Lier, R. A. W., & Pfreundschuh, M. G. (1994) · Science · doi:10.1126/science.8171337 · Cited by 156 · see citing works
Zitvogel, L., Robbins, P. D., Storkus, W. J., Clarke, M. R., Maeurer, M. J., Campbell, R. L., Davis, C., Tahara, H., Schreiber, R. D., & Lotze, M. T. (1996) · European Journal of Immunology · doi:10.1002/eji.1830260624 · Cited by 123 · see citing works
Visual inspection with acetic acid in the early detection of cervical cancer and precursors
Sankaranarayanan, R., Shyamalakumary, B., Wesley, R., Amma, N. S., Parkin, D. M., & Nair, M. K. (1999) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19990105)80:1 · Cited by 114 · see citing works
Cayeux, S., Beck, C., Aicher, A., et al. (1995) · European Journal of Immunology · doi:10.1002/eji.1830250831 · Cited by 83 · see citing works
Kroesen, B. J., Buter, J., Sleijfer, D. T., Janssen, R., van der Graaf, W., The, T., de Leij, L., & Mulder, N. (1994) · British Journal of Cancer · doi:10.1038/bjc.1994.366 · Cited by 82 · see citing works
Genes encoding a mouse monoclonal antibody are expressed in transgenic mice, rabbits and pigs
Weidle, U. H., Lenz, H., & Brem, G. (1991) · Gene · doi:10.1016/0378-1119(91)90172-8 · Cited by 79 · see citing works
Self-citationProperties of a single-chain antibody containing different linker peptides
Alfthan, K., Takkinen, K., Sizmann, D., et al. (1995) · Protein Engineering Design and Selection · doi:10.1093/protein/8.7.725 · Cited by 79 · see citing works
Can Co‐stimulated Tumor Immunity be Therapeutically Efficacious?
Hellströum, K. E., Hellström, I., & Chen, L. (1995) · Immunological Reviews · doi:10.1111/j.1600-065x.1995.tb00079.x · Cited by 77 · see citing works
Costimulatory wars: the tumor menace
Hurwitz, A. A., Kwon, E. D., & van Elsas, A. (2000) · Current Opinion in Immunology · doi:10.1016/s0952-7915(00)00147-3 · Cited by 74 · see citing works
Cytolysis of leukemic B-cells by T-cells activated via two bispecific antibodies.
Bohlen, H., Manzke, O., Patel, B., et al. (1993) · PubMed · Cited by 62 · see citing works
Target cell‐induced T cell activation with bi‐ and trispecific antibody fragments
Jung, G., Freimann, U., von Marschall, Z., Reisfeld, R. A., & Wilmanns, W. (1991) · European Journal of Immunology · doi:10.1002/eji.1830211020 · Cited by 61 · see citing works
Self-citationTibben, J. G., Boerman, O. C., Massuger, L. F. A. G., Schijf, C. P. T., Claessens, R. A. M. J., & Corstens, F. H. M. (1996) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19960516)66:4 · Cited by 60 · see citing works
Sturmhoefel, K., Lee, K., Gray, G. S., et al. (1999) · PubMed · Cited by 53 · see citing works
Notter, M., Willinger, T., Erben, U., & THIEL, E. (2001) · Blood · doi:10.1182/blood.v97.10.3138 · Cited by 49 · see citing works
Gerstmayer, B., Altenschmidt, U., Hoffmann, M., et al. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.10.4584 · Cited by 47 · see citing works
Induction of cytotoxicity in human peripheral blood mononuclear cells by monoclonal antibody OKT3.
Jung, G., Martin, D. E., & Müller‐Eberhard, H. J. (1987) · The Journal of Immunology · doi:10.4049/jimmunol.139.2.639 · Cited by 44 · see citing works
Self-citationAn in-vitro model for tumor immunotherapy with antibody heteroconjugates
Jung, G., & Eberhard, H. J. M. (1988) · Immunology Today · doi:10.1016/0167-5699(88)91304-7 · Cited by 41 · see citing works
Self-citationGuo, Y.-J., Che, X.-Y., Shen, F., Xie, T., Ma, J., Wang, X. N., Wu, S. G., Anthony, D. D., & Wu, M. C. (1997) · Nature Medicine · doi:10.1038/nm0497-451 · Cited by 40 · see citing works
Siefken, R., Klein‐Hessling, S., Serfling, E., Kurrle, R., & Schwinzer, R. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.4.1645 · Cited by 37 · see citing works
Moro, M., Gasparri, A. M., Pagano, S., Bellone, M., Tornaghi, P., Veglia, F., Corti, A., Casorati, G., & Dellabona, P. (1999) · PubMed · Cited by 28 · see citing works
Molema, G., Tervaert, J. W. C., Kroesen, B. J., et al. (2000) · British Journal of Cancer · doi:10.1054/bjoc.1999.0945 · Cited by 25 · see citing works
de Inés, C., Cochlovius, B., Schmidt, S., et al. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.7.3948 · Cited by 12 · see citing works
Bischof, A. (2000) · doi:10.1002/1521-4141(200003)30:3
Flagged first, then by citations
Cited by
Sorted by citations
Bispecific 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
Bispecific Antibodies for Cancer Immunotherapy: Current Perspectives
Müller, D., & Kontermann, R. E. (2010) · BioDrugs · doi:10.2165/11530960-000000000-00000 · Cited by 137 · see citing works
Otz, T., Große-Hovest, L., Hofmann, M., Rammensee, H.-G., & Jung, G. (2009) · Leukemia · doi:10.1038/leu.2008.271 · Cited by 38 · see citing works
Self-citationGrosse‐Hovest, L., Wick, W., Minoia, R., Weller, M., Rammensee, H., Brem, G., & Jung, G. (2005) · International Journal of Cancer · doi:10.1002/ijc.21294 · Cited by 23 · see citing works
Self-citation
- Authors
- Grosse‐Hovest, L., Hartlapp, I., Marwan, W., Brem, G., Rammensee, H., & Jung, G.
- Affiliations
- University of Tübingen (DE)
- Max Planck Society (DE)
- University of Veterinary Medicine Vienna (AT)
- Corresponding author
- Jung, Gundram
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 2003-04-22
- Volume
- 33
- Issue
- 5
- Pages
- 1334-1340
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- OpenAlex
- W1973284926
- Cited by
- 62
- References
- 31
- Citations by year
- 2026: 1 · 2025: 1 · 2022: 2 · 2021: 5 · 2019: 2 · 2018: 3 · 2017: 1 · 2016: 2 · 2015: 7 · 2014: 2 · 2013: 7 · 2012: 5
- FWCI
- 0.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- 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
- Keywords
- bispecific single-chain antibody, CD28, T cell costimulation, cancer immunotherapy, T cell activation, tumor cell killing, recombinant antibodies, tumor antigens
- MeSH terms
- Cytotoxicity, Immunologic, Humans, Lymphocyte Activation, Melanoma, Proteoglycans, Recombinant Proteins, T-Lymphocytes, Tumor Cells, Cultured, Antibodies, Bispecific, CD28 Antigens
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
