Immunoreactivity of the fully humanized therapeutic antibody PankoMab-GEX™ is an independent prognostic marker for breast cancer patients
Open accessAbstract
BACKGROUND: Mucin-1 (MUC1, CD227), more widely known as CA15-3, is an abundantly expressed epithelial cell surface antigen and has evolved to be the most predictive serum tumour marker in breast cancer. PankoMab-GEX™, which is currently being evaluated for its therapeutic efficacy in a phase IIb clinical trial, is a glyco-optimized anti-MUC1 antibody specifically recognizing a tumour-associated MUC1 epitope (TA-MUC1). The current study aimed to analyse the immunoreactivity of PankoMabGEX™ and its correlation with established clinico-pathological variables including 10-year and overall survival in a large cohort of breast cancer patients. METHODS: Breast cancer tissue sections (n = 227) underwent a standardized immunohistochemical staining protocol for TA-MUC1 by using PankoMab-GEX™ as a primary antibody. The staining was evaluated by two independent observers and quantified by applying the IR-score. RESULTS: TA-MUC1 as detected by PankoMab-GEX™ was identified in 74.9% of breast cancer tissue sections. Patients were subdivided according to the subcellular localisation of TA-MUC1 and cases classified as mem-PankoMab-GEX™ (solely membranous) positive, cyt-PankoMab-GEX™ (solely cytoplasmic) positive, double positive or as completely negative were compared regarding their survival. Herein mem-PankoMab-GEX™-positive patients performed best, while double-negative ones presented with a significantly shortened survival. Positivity for mem-PankoMab-GEX™ as well as a double-negative immunophenotype turned out to be independent prognosticators for survival. CONCLUSIONS: This is the first study to report on PankoMab-GEX™ in a large panel of breast cancer patients. The PankoMab-GEX™ epitope TA-MUC1 could be identified in the majority of cases and was found to be an independent prognosticator depending on its subcellular localisation. Since TA-MUC1 is known to be highly immunogenic cancers staining positive for PankoMab-GEX™ might be more compromised by host anti-tumour immune defence. Further, the observations reported here might be fundamental for selecting patients to undergo PankoMab-GEX™-containing chemotherapy protocols.
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?
MUC1 is overexpressed on some adenocarcinoma cells and is an important tumor surface marker, especially for breast cancer.
“MUC1 is a mucin glycoprotein overexpressed on some adenocarcinoma cells and is considered an important tumor surface marker, especially breast cancer. It has been used as a potential target for the treatment of breast cancer.250,251”
From Smart nanoparticles for cancer therapy (2023) · cites this paper as [251]
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
Harris, L. N., Fritsche, H. A., Mennel, R. G., Norton, L., Ravdin, P. M., Taube, S. E., Somerfield, M. R., Hayes, D. F., & Bast, R. C. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.2364 · Cited by 2,199 · see citing works
Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK)
McShane, L. M., Altman, D. G., Sauerbrei, W., Taube, S. E., Gion, M., & Clark, G. M. (2005) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/dji237 · Cited by 2,162 · see citing works
Krishnamurti, U., & Silverman, J. F. (2014) · Advances in Anatomic Pathology · doi:10.1097/pap.0000000000000015 · Cited by 329 · see citing works
Method for grading breast cancer.
Elston, E., & Ellis, I. O. (1993) · Journal of Clinical Pathology · doi:10.1136/jcp.46.2.189-b · Cited by 201 · see citing works
MUC1 Oncoprotein Stabilizes and Activates Estrogen Receptor α
Wei, X., Xu, H., & Kufe, D. W. (2006) · Molecular Cell · doi:10.1016/j.molcel.2005.11.030 · Cited by 186 · see citing works
PankoMab: a potent new generation anti-tumour MUC1 antibody
Danielczyk, A., Stahn, R., Faulstich, D., Löffler, A., Märten, A., Karsten, U. R., & Goletz, S. (2006) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-006-0135-9 · Cited by 127 · see citing works
Self-citationKarsten, U. R. (2004) · Glycobiology · doi:10.1093/glycob/cwh090 · Cited by 109 · see citing works
Self-citationKarsten, U. R., Diotel, C., Klich, G., et al. (1998) · PubMed · Cited by 94 · see citing works
Self-citationc-Myc and Her2 cooperate to drive a stem-like phenotype with poor prognosis in breast cancer
Nair, R., Roden, D. L., Teo, W. S., McFarland, A., Junankar, S. R., Ye, S., Nguyen, A., Yang, J. Y. H., Nikolić, I., Hui, M. N., et al. (2013) · Oncogene · doi:10.1038/onc.2013.368 · Cited by 92 · see citing works
Cao, Y., Blohm, D. H., Ghadimi, B. M., et al. (1997) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215549704501111 · Cited by 80 · see citing works
Lenhard, M., Lennerová, T., Heublein, S., et al. (2012) · BMC Cancer · doi:10.1186/1471-2407-12-553 · Cited by 78 · see citing works
Self-citationWhat Makes MUC1 a Tumor Antigen?
Karsten, U. R., von Mensdorff‐Pouilly, S., & Goletz, S. (2005) · Tumor Biology · doi:10.1159/000086956 · Cited by 78 · see citing works
Self-citationIbrahim, N. K., Yariz, K. O., Bondarenko, I., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-1151 · Cited by 71 · see citing works
Human chorionic gonadotropin and its relation to grade, stage and patient survival in ovarian cancer
Lenhard, M., Tsvilina, A., Schumacher, L., et al. (2012) · BMC Cancer · doi:10.1186/1471-2407-12-2 · Cited by 65 · see citing works
van der Vegt, B., de Roos, M. A. J., Peterse, J. L., et al. (2007) · Histopathology · doi:10.1111/j.1365-2559.2007.02757.x · Cited by 61 · see citing works
Burford, B., Gentry‐Maharaj, A., Graham, R. A., Allen, D., Pedersen, J. W., Nudelman, A. S., Blixt, O., Fourkala, E.-O., Bueti, D., Dawnay, A., et al. (2013) · British Journal of Cancer · doi:10.1038/bjc.2013.214 · Cited by 55 · see citing works
Thomsen-Friedenreich Antigen: The “Hidden” Tumor Antigen
Goletz, S., Cao, Y., Danielczyk, A., Ravn, P., Schöber, U., & Karsten, U. R. (2003) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-0065-0_10 · Cited by 44 · see citing works
Self-citationFan, X.-N., Karsten, U. R., Goletz, S., et al. (2010) · Pathology - Research and Practice · doi:10.1016/j.prp.2010.03.006 · Cited by 43 · see citing works
Self-citationGuo, Q., Tang, W., Inagaki, Y., et al. (2006) · World Journal of Gastroenterology · doi:10.3748/wjg.v12.i1.54 · Cited by 38 · see citing works
Natural and Induced Humoral Responses to MUC1
von Mensdorff‐Pouilly, S., Moreno, M., & Verheijen, R. H. M. (2011) · Cancers · doi:10.3390/cancers3033073 · Cited by 34 · see citing works
Dian, D., Janni, W. J., Kühn, C., et al. (2009) · Oncology Research and Treatment · doi:10.1159/000209280 · Cited by 29 · see citing works
MUC1c Regulates Cell Survival in Pancreatic Cancer by Preventing Lysosomal Permeabilization
Banerjee, S., Mujumdar, N. R., Dudeja, V., MacKenzie, T. N., Krosch, T. C. K., Sangwan, V., Vickers, S. M., & Saluja, A. K. (2012) · PLoS ONE · doi:10.1371/journal.pone.0043020 · Cited by 28 · see citing works
Weissenbacher, T. M., Hirte, E., Kühn, C., et al. (2013) · BMC Cancer · doi:10.1186/1471-2407-13-361 · Cited by 28 · see citing works
TA-MUC1 epitope in non-small cell lung cancer
Kuemmel, A., Single, K., Bittinger, F., et al. (2008) · Lung Cancer · doi:10.1016/j.lungcan.2008.04.005 · Cited by 26 · see citing works
MUC1 expression in canine malignant mammary tumours and relationship to clinicopathological features
Oliveira, J., Pinho, S. S., de Matos, A., et al. (2008) · The Veterinary Journal · doi:10.1016/j.tvjl.2008.09.007 · Cited by 24 · see citing works
Larrain, M. I., Demichelis, S. O., Crespo, M., et al. (2009) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/1756-9966-28-121 · Cited by 24 · see citing works
Mu, Z., Klinowska, T. C. M., Dong, X., et al. (2014) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/1756-9966-33-47 · Cited by 24 · see citing works
EMA: A Differentiation Antigen Related to Node Metastatic Capacity of Breast Carcinomas
Luna-Moré, S., Rius, F., Weil, B., et al. (2001) · Pathology - Research and Practice · doi:10.1078/0344-0338-00055 · Cited by 22 · see citing works
Dian, D., Lenhard, M., Mayr, D. C., Heublein, S., Karsten, U. R., Goletz, S., Kühn, C., Wiest, I., Friese, K., Weissenbacher, T. M., et al. (2013) · PubMed · doi:10.14670/hh-28.239 · Cited by 21 · see citing works
Self-citationJeschke, U., Wiest, I., Schumacher, A. L., et al. (2012) · PubMed · Cited by 21 · see citing works
Self-citationScholz, C., Tóth, B., Barthell, E., et al. (2009) · PubMed · doi:10.14670/hh-24.467 · Cited by 17 · see citing works
Guo, Q., Tang, W., Inagaki, Y., et al. (2007) · Oncology Reports · doi:10.3892/or.17.5.1057 · Cited by 10 · see citing works
Fukushima, M., Higuchi, K., Shimojo, H., et al. (2012) · ACTA HISTOCHEMICA ET CYTOCHEMICA · doi:10.1267/ahc.12020 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Smart nanoparticles for cancer therapy
Sun, L., Liu, H., Ye, Y., Lei, Y., Islam, R., Tan, S., Tong, R., Miao, Y.-B., & Cai, L. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01642-x · Cited by 1,073 · see citing works
- Authors
- Heublein, S., Mayr, D., Egger, M., Karsten, U., Goletz, S., Angele, M., Gallwas, J., Jeschke, U., & Ditsch, N.
- Affiliations
- Ludwig-Maximilians-Universität München (DE)
- Pathologisches Institut (DE)
- Glycotope (Germany) (DE)
- Corresponding author
- Heublein, Sabine
- Venue
- Journal of Experimental & Clinical Cancer Research
- Published
- 2015-05-19
- Volume
- 34
- Issue
- 1
- Pages
- 50-50
- ISSN
- 0392-9078 (ISSN-L)
- 1756-9966
- PMC
- PMC4447018
- OpenAlex
- W2115902453
- Cited by
- 18
- References
- 33
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 2 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 2
- FWCI
- 0.44
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Experimental & Clinical Cancer Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Keywords
- MUC1, CA15-3, breast cancer, prognostic factors, therapeutic antibodies, subcellular localization, immunoreactivity score, overall survival, patient selection for chemotherapy, antitumor immunity
- MeSH terms
- Adult, Aged, Epitopes, Antigens, Neoplasm, Antineoplastic Agents, Breast Neoplasms, Female, Humans, Middle Aged, Prognosis, Biomarkers, Tumor, Survival Analysis, Mucin-1, Neoplasm Grading, Antibodies, Monoclonal, Humanized
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