Evaluation of novel highly specific antibodies to cancer testis antigen Centrin‐1 for radioimmunoimaging and radioimmunotherapy of pancreatic cancer
Abstract Background Pancreatic ductal adenocarcinoma (PDAC) accounts for >90% of pancreatic malignancies, and has median survival of <6 months. There is an urgent need for diagnostic and therapeutic options for PDAC. Centrin1 (CETN1) is a novel member of Cancer/Testis Antigens, with a 25‐fold...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-09-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.2379 |
| _version_ | 1819115208478556160 |
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| author | Rubin Jiao Kevin J. H. Allen Mackenzie E. Malo Muath Helal Zewei Jiang Karishma Smart Susan V. Buhl David Rickles Ruth A. Bryan Ekaterina Dadachova |
| author_facet | Rubin Jiao Kevin J. H. Allen Mackenzie E. Malo Muath Helal Zewei Jiang Karishma Smart Susan V. Buhl David Rickles Ruth A. Bryan Ekaterina Dadachova |
| author_sort | Rubin Jiao |
| collection | DOAJ |
| description | Abstract Background Pancreatic ductal adenocarcinoma (PDAC) accounts for >90% of pancreatic malignancies, and has median survival of <6 months. There is an urgent need for diagnostic and therapeutic options for PDAC. Centrin1 (CETN1) is a novel member of Cancer/Testis Antigens, with a 25‐fold increase of CETN1 gene expression in PDX from PDAC patients. The absence of selective anti‐CETN1 antibodies is hampering CETN1 use for diagnosis and therapy. Here we report the generation of highly specific for CETN1 antibodies and their evaluation for radioimmunoimaging and radioimmunotherapy (RIT) of experimental PDAC. Methods The antibodies to CETN1 were generated via mice immunization with immunogenic peptide distinguishing CETN1 from CETN2. Patient tumor microarrays were used to evaluate the binding of the immune serum to PDAC versus normal pancreas. The antibodies were tested for their preferential binding to CETN1 over CETN2 by ELISA. Mice bearing PDAC MiaPaCa2 xenografts were imaged with microSPECT/CT and treated with 213Bi‐ and 177Lu‐labeled antibodies to CETN1. Results Immune serum bind to 50% PDAC cases on patient tumor microarrays with no specific binding to normal pancreas. Antibodies demonstrated preferential binding to CETN1 versus CETN2. Antibody 69‐11 localized to PDAC xenografts in mice in vivo and ex vivo. RIT of PDAC xenografts with 213Bi‐labeled antibodies was effective, safe, and CETN1‐specific. Conclusions The results demonstrate the ability of these novel antibodies to detect CETN1 both in vitro and in vivo; as well, the RIT treatment of experimental PDAC when radiolabeled with 213Bi is highly efficient and safe. Further evaluation of these novel reagents for diagnosis and treatment of PDAC is warranted. |
| first_indexed | 2024-12-22T04:57:32Z |
| format | Article |
| id | doaj.art-9ed1c8cdf1a4417bbfe386cc7289b284 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-12-22T04:57:32Z |
| publishDate | 2019-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-9ed1c8cdf1a4417bbfe386cc7289b2842022-12-21T18:38:20ZengWileyCancer Medicine2045-76342019-09-018115289530010.1002/cam4.2379Evaluation of novel highly specific antibodies to cancer testis antigen Centrin‐1 for radioimmunoimaging and radioimmunotherapy of pancreatic cancerRubin Jiao0Kevin J. H. Allen1Mackenzie E. Malo2Muath Helal3Zewei Jiang4Karishma Smart5Susan V. Buhl6David Rickles7Ruth A. Bryan8Ekaterina Dadachova9College of Pharmacy and Nutrition University of Saskatchewan Saskatoon Saskatchewan CanadaCollege of Pharmacy and Nutrition University of Saskatchewan Saskatoon Saskatchewan CanadaCollege of Pharmacy and Nutrition University of Saskatchewan Saskatoon Saskatchewan CanadaCollege of Pharmacy and Nutrition University of Saskatchewan Saskatoon Saskatchewan CanadaAlbert Einstein College of Medicine Bronx New YorkAlbert Einstein College of Medicine Bronx New YorkAlbert Einstein College of Medicine Bronx New YorkRadImmune Therapeutics Tarrytown New YorkAlbert Einstein College of Medicine Bronx New YorkCollege of Pharmacy and Nutrition University of Saskatchewan Saskatoon Saskatchewan CanadaAbstract Background Pancreatic ductal adenocarcinoma (PDAC) accounts for >90% of pancreatic malignancies, and has median survival of <6 months. There is an urgent need for diagnostic and therapeutic options for PDAC. Centrin1 (CETN1) is a novel member of Cancer/Testis Antigens, with a 25‐fold increase of CETN1 gene expression in PDX from PDAC patients. The absence of selective anti‐CETN1 antibodies is hampering CETN1 use for diagnosis and therapy. Here we report the generation of highly specific for CETN1 antibodies and their evaluation for radioimmunoimaging and radioimmunotherapy (RIT) of experimental PDAC. Methods The antibodies to CETN1 were generated via mice immunization with immunogenic peptide distinguishing CETN1 from CETN2. Patient tumor microarrays were used to evaluate the binding of the immune serum to PDAC versus normal pancreas. The antibodies were tested for their preferential binding to CETN1 over CETN2 by ELISA. Mice bearing PDAC MiaPaCa2 xenografts were imaged with microSPECT/CT and treated with 213Bi‐ and 177Lu‐labeled antibodies to CETN1. Results Immune serum bind to 50% PDAC cases on patient tumor microarrays with no specific binding to normal pancreas. Antibodies demonstrated preferential binding to CETN1 versus CETN2. Antibody 69‐11 localized to PDAC xenografts in mice in vivo and ex vivo. RIT of PDAC xenografts with 213Bi‐labeled antibodies was effective, safe, and CETN1‐specific. Conclusions The results demonstrate the ability of these novel antibodies to detect CETN1 both in vitro and in vivo; as well, the RIT treatment of experimental PDAC when radiolabeled with 213Bi is highly efficient and safe. Further evaluation of these novel reagents for diagnosis and treatment of PDAC is warranted.https://doi.org/10.1002/cam4.2379177Lutetium213Bismuthcentrin1pancreatic adenocarcinomaradioimmunotherapySPECT/CT imaging |
| spellingShingle | Rubin Jiao Kevin J. H. Allen Mackenzie E. Malo Muath Helal Zewei Jiang Karishma Smart Susan V. Buhl David Rickles Ruth A. Bryan Ekaterina Dadachova Evaluation of novel highly specific antibodies to cancer testis antigen Centrin‐1 for radioimmunoimaging and radioimmunotherapy of pancreatic cancer Cancer Medicine 177Lutetium 213Bismuth centrin1 pancreatic adenocarcinoma radioimmunotherapy SPECT/CT imaging |
| title | Evaluation of novel highly specific antibodies to cancer testis antigen Centrin‐1 for radioimmunoimaging and radioimmunotherapy of pancreatic cancer |
| title_full | Evaluation of novel highly specific antibodies to cancer testis antigen Centrin‐1 for radioimmunoimaging and radioimmunotherapy of pancreatic cancer |
| title_fullStr | Evaluation of novel highly specific antibodies to cancer testis antigen Centrin‐1 for radioimmunoimaging and radioimmunotherapy of pancreatic cancer |
| title_full_unstemmed | Evaluation of novel highly specific antibodies to cancer testis antigen Centrin‐1 for radioimmunoimaging and radioimmunotherapy of pancreatic cancer |
| title_short | Evaluation of novel highly specific antibodies to cancer testis antigen Centrin‐1 for radioimmunoimaging and radioimmunotherapy of pancreatic cancer |
| title_sort | evaluation of novel highly specific antibodies to cancer testis antigen centrin 1 for radioimmunoimaging and radioimmunotherapy of pancreatic cancer |
| topic | 177Lutetium 213Bismuth centrin1 pancreatic adenocarcinoma radioimmunotherapy SPECT/CT imaging |
| url | https://doi.org/10.1002/cam4.2379 |
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