Data from A Novel Therapeutic Strategy for Pancreatic Cancer: Targeting Cell Surface Glycan Using rBC2LC-N Lectin–Drug Conjugate (LDC) Article Swipe
Osamu Shimomura
,
Tatsuya Oda
,
Hiroaki Tateno
,
Yusuke Ozawa
,
Sota Kimura
,
Shingo Sakashita
,
Masayuki Noguchi
,
Jun Hirabayashi
,
Makoto Asashima
,
Nobuhiro Ohkohchi
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1158/1535-7163.c.6539581.v1
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1158/1535-7163.c.6539581.v1
Various cancers, including pancreatic ductal adenocarcinoma (PDAC), remain intractable even with costly tumor-targeting antibody drugs. Because the outermost coatings of cancer cells are composed of cell-specific glycan layers (glycocalyx), lectins, proteins with glycan-binding potential, were evaluated for possible use as drug carriers in PDAC treatment. A human PDAC cell line with well-to-moderately differentiated properties (Capan-1) was subjected to lectin microarray analysis to identify specific lectin–glycan pairs. The selected lectin was fused with a bacterial exotoxin for the construction of a lectin–drug conjugate (LDC), and its safety and antitumor effects were evaluated. A specific affinity between a recombinant bacterial C-type lectin (rBC2LC-N) and Capan-1 was identified, and its positivity was confirmed in 69 human samples. In contrast to the belief that all lectins mediate harmful hemagglutination, rBC2LC-N did not cause hemagglutination with human erythrocytes and was safely administered to mice. The 50% inhibitory concentration of LDC to Capan-1 (1.04 pg/mL = 0.0195 pmol/L) was 1/1,000 lower than that reported for conventional immunotoxins. The intraperitoneal administration of LDC reduced the tumor weight from 390 to 130.8 mg (P < 0.01) in an orthotopic model and reduced the number of nodules from 48 to 3 (P < 0.001) and improved survival from 62 to 105 days in a peritoneal dissemination model (P < 0.0001). In addition, the effect of LDC was reproduced in nodules from patient-derived PDAC xenografts through intravenous injection. Herein, we show the concept of utilizing lectins as drug carriers to target glycans on the cancer cell surface, highlighting new insights into cancer treatments. Mol Cancer Ther; 17(1); 183–95. ©2017 AACR.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1158/1535-7163.c.6539581.v1
- OA Status
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- Related Works
- 10
- OpenAlex ID
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All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4362567744Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1158/1535-7163.c.6539581.v1Digital Object Identifier
- Title
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Data from A Novel Therapeutic Strategy for Pancreatic Cancer: Targeting Cell Surface Glycan Using rBC2LC-N Lectin–Drug Conjugate (LDC)Work title
- Type
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preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-04-03Full publication date if available
- Authors
-
Osamu Shimomura, Tatsuya Oda, Hiroaki Tateno, Yusuke Ozawa, Sota Kimura, Shingo Sakashita, Masayuki Noguchi, Jun Hirabayashi, Makoto Asashima, Nobuhiro OhkohchiList of authors in order
- Landing page
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https://doi.org/10.1158/1535-7163.c.6539581.v1Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
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goldOpen access status per OpenAlex
- OA URL
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https://doi.org/10.1158/1535-7163.c.6539581.v1Direct OA link when available
- Concepts
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Lectin, Glycan, Chemistry, Immunotoxin, Conjugate, Pancreatic cancer, Molecular biology, Cancer research, Pharmacology, Cancer, Biology, Cytotoxicity, In vitro, Medicine, Biochemistry, Internal medicine, Glycoprotein, Mathematical analysis, MathematicsTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.tumor | 168 |
| abstract_inverted_index.(LDC), | 82 |
| abstract_inverted_index.0.001) | 194 |
| abstract_inverted_index.0.0195 | 150 |
| abstract_inverted_index.17(1); | 256 |
| abstract_inverted_index.C-type | 98 |
| abstract_inverted_index.Cancer | 254 |
| abstract_inverted_index.belief | 118 |
| abstract_inverted_index.cancer | 20, 244, 251 |
| abstract_inverted_index.costly | 11 |
| abstract_inverted_index.drugs. | 14 |
| abstract_inverted_index.ductal | 4 |
| abstract_inverted_index.effect | 214 |
| abstract_inverted_index.glycan | 26 |
| abstract_inverted_index.layers | 27 |
| abstract_inverted_index.lectin | 58, 68, 99 |
| abstract_inverted_index.number | 185 |
| abstract_inverted_index.pairs. | 65 |
| abstract_inverted_index.remain | 7 |
| abstract_inverted_index.safely | 135 |
| abstract_inverted_index.safety | 85 |
| abstract_inverted_index.target | 240 |
| abstract_inverted_index.weight | 169 |
| abstract_inverted_index.©2017 | 258 |
| abstract_inverted_index.(PDAC), | 6 |
| abstract_inverted_index.1/1,000 | 153 |
| abstract_inverted_index.Because | 15 |
| abstract_inverted_index.Capan-1 | 102, 146 |
| abstract_inverted_index.Herein, | 228 |
| abstract_inverted_index.between | 94 |
| abstract_inverted_index.concept | 232 |
| abstract_inverted_index.effects | 88 |
| abstract_inverted_index.glycans | 241 |
| abstract_inverted_index.harmful | 123 |
| abstract_inverted_index.lectins | 121, 235 |
| abstract_inverted_index.mediate | 122 |
| abstract_inverted_index.nodules | 187, 220 |
| abstract_inverted_index.pmol/L) | 151 |
| abstract_inverted_index.reduced | 166, 183 |
| abstract_inverted_index.through | 225 |
| abstract_inverted_index.0.0001). | 210 |
| abstract_inverted_index.affinity | 93 |
| abstract_inverted_index.analysis | 60 |
| abstract_inverted_index.antibody | 13 |
| abstract_inverted_index.cancers, | 1 |
| abstract_inverted_index.carriers | 41, 238 |
| abstract_inverted_index.coatings | 18 |
| abstract_inverted_index.composed | 23 |
| abstract_inverted_index.contrast | 115 |
| abstract_inverted_index.exotoxin | 74 |
| abstract_inverted_index.identify | 62 |
| abstract_inverted_index.improved | 196 |
| abstract_inverted_index.insights | 249 |
| abstract_inverted_index.lectins, | 29 |
| abstract_inverted_index.possible | 37 |
| abstract_inverted_index.proteins | 30 |
| abstract_inverted_index.rBC2LC-N | 125 |
| abstract_inverted_index.reported | 157 |
| abstract_inverted_index.samples. | 113 |
| abstract_inverted_index.selected | 67 |
| abstract_inverted_index.specific | 63, 92 |
| abstract_inverted_index.surface, | 246 |
| abstract_inverted_index.survival | 197 |
| abstract_inverted_index.(Capan-1) | 54 |
| abstract_inverted_index.183–95. | 257 |
| abstract_inverted_index.addition, | 212 |
| abstract_inverted_index.antitumor | 87 |
| abstract_inverted_index.bacterial | 73, 97 |
| abstract_inverted_index.confirmed | 109 |
| abstract_inverted_index.conjugate | 81 |
| abstract_inverted_index.evaluated | 35 |
| abstract_inverted_index.including | 2 |
| abstract_inverted_index.outermost | 17 |
| abstract_inverted_index.subjected | 56 |
| abstract_inverted_index.utilizing | 234 |
| abstract_inverted_index.(rBC2LC-N) | 100 |
| abstract_inverted_index.evaluated. | 90 |
| abstract_inverted_index.inhibitory | 141 |
| abstract_inverted_index.injection. | 227 |
| abstract_inverted_index.microarray | 59 |
| abstract_inverted_index.orthotopic | 180 |
| abstract_inverted_index.pancreatic | 3 |
| abstract_inverted_index.peritoneal | 205 |
| abstract_inverted_index.positivity | 107 |
| abstract_inverted_index.potential, | 33 |
| abstract_inverted_index.properties | 53 |
| abstract_inverted_index.reproduced | 218 |
| abstract_inverted_index.treatment. | 44 |
| abstract_inverted_index.xenografts | 224 |
| abstract_inverted_index.identified, | 104 |
| abstract_inverted_index.intractable | 8 |
| abstract_inverted_index.intravenous | 226 |
| abstract_inverted_index.recombinant | 96 |
| abstract_inverted_index.treatments. | 252 |
| abstract_inverted_index.<i>Mol | 253 |
| abstract_inverted_index.administered | 136 |
| abstract_inverted_index.construction | 77 |
| abstract_inverted_index.conventional | 159 |
| abstract_inverted_index.erythrocytes | 132 |
| abstract_inverted_index.highlighting | 247 |
| abstract_inverted_index.(glycocalyx), | 28 |
| abstract_inverted_index.cell-specific | 25 |
| abstract_inverted_index.concentration | 142 |
| abstract_inverted_index.dissemination | 206 |
| abstract_inverted_index.immunotoxins. | 160 |
| abstract_inverted_index.lectin–drug | 80 |
| abstract_inverted_index.adenocarcinoma | 5 |
| abstract_inverted_index.administration | 163 |
| abstract_inverted_index.differentiated | 52 |
| abstract_inverted_index.glycan-binding | 32 |
| abstract_inverted_index.intraperitoneal | 162 |
| abstract_inverted_index.lectin–glycan | 64 |
| abstract_inverted_index.patient-derived | 222 |
| abstract_inverted_index.tumor-targeting | 12 |
| abstract_inverted_index.hemagglutination | 129 |
| abstract_inverted_index.hemagglutination, | 124 |
| abstract_inverted_index.well-to-moderately | 51 |
| abstract_inverted_index.(<i>P</i> | 175, 192, 208 |
| abstract_inverted_index.<div>Abstract<p>Various | 0 |
| abstract_inverted_index.AACR</i>.</p></div> | 259 |
| cited_by_percentile_year | |
| countries_distinct_count | 0 |
| institutions_distinct_count | 10 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.8299999833106995 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.13179471 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |