The DOI matches its Crossref record; 32 of the 34 references it cites were found in a registry or an index.
Induction of a long-lasting antitumor immunity by a trifunctional bispecific antibody
Abstract
Bispecific antibodies (bsAbs) can efficiently mediate tumor cell killing by redirecting preactivated or costimulated T cells to disseminated tumor cells, especially in a minimal residual disease situation. This study demonstrates that the trifunctional bsAb BiLu is able to kill tumor cells very efficiently without any additional costimulation of effector cells in vitro and in vivo. Remarkably, this bsAb also induces a long-lasting protective immunity against the targeted syngeneic mouse tumors (B16 melanoma and A20 B-cell lymphoma, respectively). A strong correlation was observed between the induction of a humoral immune response with tumor-reactive antibodies and the survival of mice. This humoral response was at least in part tumor specific as shown in the A20 model by the detection of induced anti-idiotype antibodies. Both the survival of mice and antitumor titers were significantly diminished when F(ab′)2 fragments of the same bsAb were applied, demonstrating the importance of the Fc region in this process. With the use of T-cell depletion, a contribution of a cellular antitumor response could be demonstrated. These results reveal the necessity of the Fc region of the bsAb with its potent immunoglobulin subclass combination mouse immunoglobulin G2a (IgG2a) and rat IgG2b. The antigen-presenting system seems to be crucial for achieving an efficient tumor cell killing and induction of long-lasting antitumor immunity. Hereby, the recruitment and activation of accessory cells by the intact bsAb is essential.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“In animal studies, 100% of mice administered an injection of 4 μg of triomabs survived after intraperitoneal (IP) injection of a lethal dose of EpCAM + melanoma cells. 25”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [25]
In the citing paper
“All mice rechallenged on day 144 after the primary challenge were still able to reject the tumor, indicating the high efficacy and long duration of the antitumor response.”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [25]
In the citing paper
“This effect was dependent on the presence of the hybrid Fc, and involved a humoral response directed against the non-transfected (EPCAM -) tumor cells.”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [25]
Citations
Cites
1 retracted
Kugler, A., Stuhler, G., Walden, P., Zöller, G., Zobywalski, A., Brossart, P., Trefzer, U., Ullrich, S., Müller, C. A., Becker, V., et al. (2000) · Nature Medicine · doi:10.1038/73193 · Cited by 637
RetractedDranoff, G., Jaffee, E. M., Lazenby, A., Golumbek, P. T., Levitsky, H., Brose, K., Jackson, V., Hamada, H., Pardoll, D. M., & Mulligan, R. C. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.8.3539 · Cited by 2,820
Bendandi, M., Gocke, C. D., Kobrin, C. B., Benko, F. A., Sternas, L. A., Pennington, R., Watson, T. M., Reynolds, C. W., Gause, B. L., Duffey, P. L., et al. (1999) · Nature Medicine · doi:10.1038/13928 · Cited by 591
Induction of antitumor activity by immunization with fusions of dendritic and carcinoma cells
Gong, J., Chen, D., Kashiwaba, M., & Kufe, D. W. (1997) · Nature Medicine · doi:10.1038/nm0597-558 · Cited by 591
Ep-CAM: a human epithelial antigen is a homophilic cell-cell adhesion molecule.
Litvinov, S. V., Velders, M. P., Bakker, H. A. M., Fleuren, G. J., & Warnaar, S. O. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.125.2.437 · Cited by 525
CD40 antibody evokes a cytotoxic T-cell response that eradicates lymphoma and bypasses T-cell help
French, R. R., Chan, H. T. C., Tutt, A. L., & Glennie, M. J. (1999) · Nature Medicine · doi:10.1038/8426 · Cited by 426
Lindhofer, H., Mocikat, R., Steipe, B., & Thierfelder, S. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.155.1.219 · Cited by 213
Self-citationZeidler, R., Reisbach, G., Wollenberg, B., Lang, S., Chaubal, S., Schmitt, B., & Lindhofer, H. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.3.1246 · Cited by 204
Self-citationHeo, D. S., Park, J. G., Hata, K., Day, R., Herberman, R. B., & Whiteside, T. L. (1990) · PubMed · Cited by 192
Zeidler, R., Mysliwietz, J., Csánady, M., Walz, A., Ziegler, I., Schmitt, B., Wollenberg, B., & Lindhofer, H. (2000) · British Journal of Cancer · doi:10.1054/bjoc.2000.1237 · Cited by 189
Self-citation
Cited by
Sorted by citations
Items 101–174 of 174
The evolving role of catumaxomab in gastric cancer
Lordick, F., Ott, K., Weitz, J., & Jäger, D. (2008) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.8.9.1407 · Cited by 14
The bi-specific CD3 × NCAM antibody: a model to preactivate T cells prior to tumour cell lysis
JENSEN, M., Ernestus, K., Kemshead, J. T., Klehr, M., von Bergwelt‐Baildon, M. S., Schinköthe, T., Schultze, J. L., & Berthold, F. (2003) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.2003.02300.x · Cited by 14
Gronau, S., Schmitt, M. W., Thess, B., Reinhardt, P., Wiesneth, M., Schmitt, A., & Riechelmann, H. (2005) · Head & Neck · doi:10.1002/hed.20170 · Cited by 14
Pietzner, K., Jäger, M., Schoberth, A., Oskay-Özcelik, G., Kuhberg, M., Lindhofer, H., & Sehouli, J. (2011) · Medical Oncology · doi:10.1007/s12032-011-9961-5 · Cited by 13
Self-citationEpothilone B enhances surface EpCAM expression in ovarian cancer Hey cells
Shahabi, S., Yang, C. H., Goldberg, G. L., & Horwitz, S. B. (2010) · Gynecologic Oncology · doi:10.1016/j.ygyno.2010.07.005 · Cited by 13
Immunotherapy of Peritoneal Carcinomatosis
Ströhlein, M. A., & Heiss, M. M. (2007) · Springer eBooks · doi:10.1007/978-0-387-48993-3_33 · Cited by 13
Targeting Human Cancer Stem Cells with Monoclonal Antibodies
Naujokat, C. (2012) · Journal of Clinical & Cellular Immunology · doi:10.4172/2155-9899.s5-007 · Cited by 13
Systemic effect of catumaxomab in a patient with metastasized colorectal cancer: a case report
Bezan, A., Hohla, F., Meißnitzer, T., & Greil, R. (2013) · BMC Cancer · doi:10.1186/1471-2407-13-618 · Cited by 12
Trifunctional Triomab® Antibodies for Cancer Therapy
Lindhofer, H., Heß, J., & Ruf, P. (2011) · Springer eBooks · doi:10.1007/978-3-642-20910-9_16 · Cited by 12
Self-citation5th European Antibody Congress 2009
Beck, A., Reichert, J. M., & Wurch, T. (2010) · mAbs · doi:10.4161/mabs.2.2.11302 · Cited by 12
Thompson, S., Dessi, J. L., & Self, C. H. (2009) · mAbs · doi:10.4161/mabs.1.4.9045 · Cited by 11
Deppisch, N., Ruf, P., Eißler, N., Lindhofer, H., & Mocikat, R. (2016) · Oncotarget · doi:10.18632/oncotarget.13888 · Cited by 11
Self-citationTargeted immunotherapy of cancer: development of antibody-induced cellular immunity
Lu, Y. J., & Low, P. S. (2003) · Journal of Pharmacy and Pharmacology · doi:10.1211/002235702540 · Cited by 11
Control of Malaria by Bio-Therapeutics and Drug Delivery Systems
Qaraghuli, M. M. A., Obeid, M. A., Aldulaimi, O., & Ferro, V. A. (2017) · Journal of Medical Microbiology & Diagnosis · doi:10.4172/2161-0703.1000260 · Cited by 10
Kotani, N., Yamaguchi, A., Ohnishi, T., Kuwahara, R., Nakano, T., Nakano, Y., Ida, Y., Murakoshi, T., & Honke, K. (2019) · Cancer Science · doi:10.1111/cas.14108 · Cited by 10
Ströhlein, M. A., & Heiss, M. M. (2012) · Der Onkologe · doi:10.1007/s00761-012-2287-x · Cited by 10
Re-challenge with catumaxomab in patients with malignant ascites: results from the SECIMAS study
Pietzner, K., Vergote, I. B., Santoro, A., Chekerov, R., Marmé, F., Rosenberg, P., Martinius, H., Friccius-Quecke, H., & Sehouli, J. (2014) · Medical Oncology · doi:10.1007/s12032-014-0308-x · Cited by 10
Antitumour effects of a bispecific trivalent antibody in multicellular tumour spheroids.
Walz, A., Mack, B., Schmitt, B., Gires, O., Wollenberg, B., & Zeidler, R. (2004) · PubMed · Cited by 10
Müller, D., & Kontermann, R. E. (2007) · Wiley eBooks · doi:10.1002/9783527619740.ch15 · Cited by 10
Ströhlein, M. A., & Heiss, M. M. (2009) · Journal of Surgical Oncology · doi:10.1002/jso.21338 · Cited by 8
Eißler, N., Mysliwietz, J., Deppisch, N., Ruf, P., Lindhofer, H., & Mocikat, R. (2013) · Molecular Medicine · doi:10.2119/molmed.2012.00140 · Cited by 8
Self-citationNovel Antineoplastics Targeting Genetic Changes in Colorectal Cancer
Joudeh, J., Allen, J. E., Das, A., Prabhu, V. V., Farbaniec, M., Adler, J. M., & El‐Deiry, W. S. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-6176-0_1 · Cited by 8
Thompson, S., Dessi, J. L., & Self, C. H. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.11.158 · Cited by 8
Müller, D., & Kontermann, R. E. (2014) · Wiley eBooks · doi:10.1002/9783527682423.ch11 · Cited by 9
Bispecific Antibodies: Developments and Current Perspectives
Kontermann, R. E. (2011) · Springer eBooks · doi:10.1007/978-3-642-20910-9_1 · Cited by 7
Novel therapeutics in breast cancer—Looking to the future
Vora, T. S., de Azambuja, E., Awada, A. H., & Piccart, M. J. (2009) · Update on Cancer Therapeutics · doi:10.1016/j.uct.2009.07.001 · Cited by 7
The Role of the Immune System in Ovarian Cancer and Implications on Therapy
Menderes, G., Schwab, C. L., Black, J., & Santin, A. D. (2016) · Expert Review of Clinical Immunology · doi:10.1586/1744666x.2016.1147957 · Cited by 7
Bispecific Antibodies from Hybrid Hybridoma
Moldenhauer, G. (2011) · Springer eBooks · doi:10.1007/978-3-642-20910-9_2 · Cited by 7
Proteomic Investigation of Immune Checkpoints and Some of Their Inhibitors
Agostini, M., Traldi, P., & Hamdan, M. H. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25179276 · Cited by 6
Metzger, O., Vora, T. S., & Awada, A. H. (2010) · Expert Opinion on Investigational Drugs · doi:10.1517/13543781003730135 · Cited by 6
Schönberger, S., Kraft, D., Nettersheim, D., Schorle, H., Casati, A., Craveiro, R. B., Mohseni, M. M., Calaminus, G., & Dilloo, D. (2020) · Cancers · doi:10.3390/cancers12051279 · Cited by 6
Walz, A., Andratschke, M., Wollenberg, B., Lindhofer, H., & Zeidler, R. (2005) · PubMed · Cited by 6
Self-citationKrawczyk, M. J., Zimmermann, S., Vidacek, D., & Lammert, F. (2012) · Onkologie · doi:10.1159/000342670 · Cited by 5
Immune response and locoregional treatments for peritoneal carcinomatosis
Fiorentini, C., Sarti, D., Guadagni, S., & Fiorentini, G. (2022) · International review of cytology · doi:10.1016/bs.ircmb.2022.04.016 · Cited by 5
Cancer: Immunology and Immunotharapy
Chhajed, S. S., Mali, M. V., Shaikh, A. Z., Pawar, S., & Jain, R. S. (2022) · Research Journal of Pharmacology and Pharmacodynamics · doi:10.52711/2321-5836.2022.00027 · Cited by 5
Biothérapies: évolution ou révolution?
Sibilia, J. (2006) · La Presse Médicale · doi:10.1016/s0755-4982(06)74656-5 · Cited by 5
Lasting remission following multimodal treatment in a patient with metastatic breast cancer
Stemmler, H., Menzel, H., Salat, C., Lindhofer, H., Kahlert, S., Heinemann, V., & Kolb, H. J. (2005) · Anti-Cancer Drugs · doi:10.1097/01.cad.0000180122.24031.13 · Cited by 4
Self-citationNew Treatment Modalities for the Management of Peritoneal Metastases
Bhatt, A., & Mehta, A. (2017) · Springer eBooks · doi:10.1007/978-981-10-7053-2_20 · Cited by 4
Lum, L. G., & Al-Kadhimi, Z. S. (2008) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.3.9.1081 · Cited by 4
Locoregional and Palliative Therapies for Patients with Unresectable Peritoneal Metastases
Katdare, N., Prabhu, R., & Bhatt, A. (2017) · Springer eBooks · doi:10.1007/978-981-10-7053-2_22 · Cited by 3
Smaglo, B. G., Aldeghaither, D. S., & Weiner, L. M. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-374279-7.17021-3 · Cited by 4
Catumaxomab in the Treatment of Malignant Ascites: The Evidence of its Therapeutic Value
Wimberger, P., Heubner, M. L., & Kimmig, R. (2010) · Clinical Medicine Insights Therapeutics · doi:10.4137/cmt.s4954 · Cited by 2
Prädiktive Faktoren in der metastasierten Situation
Battista, M., Stickeler, E., & Schmidt, M. (2015) · Der Gynäkologe · doi:10.1007/s00129-015-3803-z · Cited by 2
Acid pH promotes bispecific antibody formation by the redox procedure
Gupta, J., Hoque, M., Ahmad, M. F., Khan, R. H., & Saleemuddin, M. (2018) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2018.12.063 · Cited by 2
Clinical Application of Therapeutic Bispecific Antibodies
Belachew, G. T. (2023) · Biomedical Journal of Scientific & Technical Research · doi:10.26717/bjstr.2023.49.007880 · Cited by 1
Molecular staging of cancer: Concepts of today, therapies of tomorrow
Allgayer, H. (2003) · Journal of Surgical Oncology · doi:10.1002/jso.10226 · Cited by 2
Les biothérapies immunomodulatrices: Une révolution thérapeutique dans les maladies auto-immunes
Sibilia, J. (2006) · Revue Francophone des Laboratoires · doi:10.1016/s1773-035x(06)80321-7 · Cited by 1
Producing and prospects for the use of bispecific antibodies for the treatment of cancer
Sedykh, S. E., & Nevinsky, G. A. (2019) · Advances in molecular oncology · doi:10.17650/2313-805x-2018-5-4-30-40 · Cited by 1
Monoclonal Antibodies for the Treatment of Cancer
Weiner, L. M., & Surana, R. (2015) · Elsevier eBooks · doi:10.1016/b978-1-4557-4066-6.00050-0 · Cited by 1
Naissance et développement de l’immunothérapie ciblée : La révolution des biomédicaments
Sibilia, J. (2007) · Revue du Rhumatisme · doi:10.1016/s1169-8330(07)80611-9 · Cited by 1
Ströhlein, M. A., Grützner, K. U., Lordick, F., Rüttinger, D., Peschel, C., Jauch, K. ‐., Schemanski, O. C., & Heiss, M. M. (2006) · Langenbecks Archiv für Chirurgie. Supplement · doi:10.1007/3-540-34668-6_155
Chimiothérapie intra-ascitique palliative
Dufour, P. (2006) · Springer eBooks · doi:10.1007/2-287-30921-7_31
Lindhofer, H., Stanglmaier, M., Buhmann, R., Jäger, M., Klunker, D., Ruf, P., & Heß, J. (2014) · doi:10.1002/9783527682423.ch51
Self-citationLum, L. G., & Yang, W. (2007) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.17.4.459
Bifunctional Antibodies: Preclinical and Clinical Applications
Shuptrine, C. W., & Weiner, L. M. (2013) · Springer eBooks · doi:10.1007/978-1-4614-8809-5_10
Vers l'utilisation des Immunoglobulines A humaines ou de leurs variants à des fins thérapeutiques
Pascal, V. (2009) · OpenGrey (Institut de l'Information Scientifique et Technique)
Principles of Targeted Immunotherapy
Baumeister, S. H. C., & Dranoff, G. (2015) · Wiley eBooks · doi:10.1002/9781118468678.ch3
Antikörpertherapie in klinischer und präklinischer Anwendung bei gastrointestinalen Karzinomen
Thalheimer, A., Brändlein, S., Vollmers, P., Thiede, A., Meyer, D., & Illert, B. (2007) · Der Onkologe · doi:10.1007/s00761-007-1190-3
Ströhlein, M. A., Grützner, K. U., Lordick, F., Rüttinger, D., Peschel, C., Jauch, K. ‐., Schemanski, O. C., & Heiss, M. M. (2006)
Jäger, M., Schoberth, A., & Ruf, P. (2009)
Self-citationThe Future in Ovarian Cancer: Advances in Immunotherapies
Makkouk, A., Chester, C., & Kohrt, H. E. K. (2016) · Springer eBooks · doi:10.1007/978-3-319-32110-3_11
Groth, A. (2010) · heiDOK (Heidelberg University) · doi:10.11588/heidok.00010763
Ströhlein, M. A. (2018) · Springer eBooks · doi:10.1007/978-3-662-54500-3_30
Lukka, P. B., Wagh, S., & Meibohm, B. (2019) · Wiley eBooks · doi:10.1002/9781119289234.ch9
Ströhlein, M. A., Jäger, M., Lindhofer, H., Jauch, K. ‐., & Heiss, M. M. (2003) · Langenbecks Archiv für Chirurgie. Supplement · doi:10.1007/978-3-642-19024-7_34
Self-citationKépénékian, V., Villeneuve, L., & Gléhen, O. (2020) · Côlon & Rectum · doi:10.3166/cer-2020-0163
IPEC, HIPEC, Bidirectional Chemotherapy, and Immunotherapy in Aggressive Peritoneal Metastasis
Ströhlein, M. A. (2021) · Springer eBooks · doi:10.1007/978-3-030-62640-2_30
Immunotherapy of peritoneal carcinomatosis
Ströhlein, M. A., & Heiss, M. M. (2015) · CRC Press eBooks · doi:10.1201/b19409-40
Woodford, R. G., & Lim, K. H. J. (2025) · Elsevier eBooks · doi:10.1016/b978-0-12-824465-4.00236-2
Der trifunktionale Antikörper Catumaxomab
Marmé, F. (2011) · Der Gynäkologe · doi:10.1007/s00129-011-2849-9
Ströhlein, M. A., Jäger, M., Lindhofer, H., Jauch, K. ‐., & Heiss, M. M. (2005) · Springer eBooks · doi:10.1007/3-540-26560-0_29
Self-citationEissler, N., Mysliwietz, J., Deppisch, N., Ruf, P., Lindhofer, H., & Mocikat, R. (2013) · Figshare · doi:10.6084/m9.figshare.7193762
Self-citationBiodegradable microparticles for in situ immunization against cancer
Makkouk, A., Norian, L. A., Monick, M., Weiner, G. J., Lubaroff, D., & Salem, A. (2014) · doi:10.17077/etd.sl8jfuqu
Surgical Trials for Gastric Cancer
Reim, D., Novotny, A., & Schuhmacher, C. P. (2015) · Springer eBooks · doi:10.1007/978-3-319-15826-6_20
Metadata
- Authors
- Ruf, P., & Lindhofer, H.
- Affiliations
- Helmholtz Munich (DE)
- ORCID
- Ruf, Peter
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2001-10-15
- Volume
- 98
- Issue
- 8
- Pages
- 2526-2534
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1972848082
- Cited by
- 174
- References
- 34
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 6 · 2020: 2 · 2019: 5 · 2018: 3 · 2017: 4 · 2016: 11 · 2015: 9 · 2014: 15 · 2013: 9 · 2012: 16
- FWCI
- 2.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Site cant be reached (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- bispecific antibodies, trifunctional antibody, antitumor immunity, Fc fragment, humoral immune response, anti-idiotypic antibodies, T cell depletion, antigen-presenting cells, B16 melanoma, tumor cell killing, immunoglobulin G2a, tumor-specific antibodies
- MeSH terms
- Animals, Antibodies, Neoplasm, Antibody Formation, Antibody Specificity, Cytotoxicity, Immunologic, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Immunoglobulin G, Immunoglobulin Idiotypes, Immunoglobulin Fab Fragments, Immunoglobulin Fc Fragments, Melanoma, Experimental, Mice, Inbred BALB C, Mice, Inbred C57BL, Survival Rate, Antibodies, Bispecific, Mice, Rats
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
