Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer

Autores
Sarduy, M. R.; García, I.; Coca, M. A.; Perera, A.; Torres, L. A.; Valenzuela, C. M.; Baladrón, I.; Solares, M.; Reyes, V.; Hernández, I.; Perera, Y.; Martínez, Y. M.; Molina, L.; González, Y. M.; Ancízar, J. A.; Prats, A.; González, L.; Casacó, C. A.; Acevedo, B. E.; López Saura, P. A.; Alonso, Daniel Fernando; Gómez, R.; Perea Rodríguez, S. E.
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background:We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose.Methods:Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using 99 Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry.Results:Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1±8.9 vs 31.3±12.9 mg (P=0.01). Both, AUC 24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P<0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P=0.03) in tumour specimens.Conclusion:Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.
Fil: Sarduy, M. R.. Medical-surgical Research Center; Cuba
Fil: García, I.. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Coca, M. A.. Clinical Investigation Center; Cuba
Fil: Perera, A.. Clinical Investigation Center; Cuba
Fil: Torres, L. A.. Clinical Investigation Center; Cuba
Fil: Valenzuela, C. M.. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Baladrón, I.. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Solares, M.. Hospital Materno Ramón González Coro; Cuba
Fil: Reyes, V.. Center For Genetic Engineering And Biotechnology Havana; Cuba
Fil: Hernández, I.. Isotope Center; Cuba
Fil: Perera, Y.. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Martínez, Y. M.. Medical-surgical Research Center; Cuba
Fil: Molina, L.. Medical-surgical Research Center; Cuba
Fil: González, Y. M.. Medical-surgical Research Center; Cuba
Fil: Ancízar, J. A.. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Prats, A.. Clinical Investigation Center; Cuba
Fil: González, L.. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Casacó, C. A.. Clinical Investigation Center; Cuba
Fil: Acevedo, B. E.. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: López Saura, P. A.. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes; Argentina
Fil: Gómez, R.. Elea Laboratories; Argentina
Fil: Perea Rodríguez, S. E.. Center For Genetic Engineering And Biotechnology Havana; Cuba. Centro de Ingeniería Genética y Biotecnología; Cuba
Materia
B23/NUCLEOPHOSMIN
CERVICAL CANCER
CIGB-300
TUMOUR UPTAKE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/96176
Acceder
id CONICETDig_4a948fff2502d46e7e6fa36c9b046ecf
oai_identifier_str oai:ri.conicet.gov.ar:11336/96176
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancerSarduy, M. R.García, I.Coca, M. A.Perera, A.Torres, L. A.Valenzuela, C. M.Baladrón, I.Solares, M.Reyes, V.Hernández, I.Perera, Y.Martínez, Y. M.Molina, L.González, Y. M.Ancízar, J. A.Prats, A.González, L.Casacó, C. A.Acevedo, B. E.López Saura, P. A.Alonso, Daniel FernandoGómez, R.Perea Rodríguez, S. E.B23/NUCLEOPHOSMINCERVICAL CANCERCIGB-300TUMOUR UPTAKEhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Background:We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose.Methods:Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using 99 Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry.Results:Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1±8.9 vs 31.3±12.9 mg (P=0.01). Both, AUC 24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P<0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P=0.03) in tumour specimens.Conclusion:Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.Fil: Sarduy, M. R.. Medical-surgical Research Center; CubaFil: García, I.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Coca, M. A.. Clinical Investigation Center; CubaFil: Perera, A.. Clinical Investigation Center; CubaFil: Torres, L. A.. Clinical Investigation Center; CubaFil: Valenzuela, C. M.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Baladrón, I.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Solares, M.. Hospital Materno Ramón González Coro; CubaFil: Reyes, V.. Center For Genetic Engineering And Biotechnology Havana; CubaFil: Hernández, I.. Isotope Center; CubaFil: Perera, Y.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Martínez, Y. M.. Medical-surgical Research Center; CubaFil: Molina, L.. Medical-surgical Research Center; CubaFil: González, Y. M.. Medical-surgical Research Center; CubaFil: Ancízar, J. A.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Prats, A.. Clinical Investigation Center; CubaFil: González, L.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Casacó, C. A.. Clinical Investigation Center; CubaFil: Acevedo, B. E.. Centro de Ingeniería Genética y Biotecnología; CubaFil: López Saura, P. A.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes; ArgentinaFil: Gómez, R.. Elea Laboratories; ArgentinaFil: Perea Rodríguez, S. E.. Center For Genetic Engineering And Biotechnology Havana; Cuba. Centro de Ingeniería Genética y Biotecnología; CubaNature Publishing Group2015-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/96176Sarduy, M. R.; García, I.; Coca, M. A.; Perera, A.; Torres, L. A.; et al.; Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer; Nature Publishing Group; British Journal Of Cancer; 112; 10; 5-2015; 1636-16430007-0920CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/bjc2015137info:eu-repo/semantics/altIdentifier/doi/10.1038/bjc.2015.137info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:06:26Zoai:ri.conicet.gov.ar:11336/96176instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:06:26.488CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer
title Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer
spellingShingle Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer
Sarduy, M. R.
B23/NUCLEOPHOSMIN
CERVICAL CANCER
CIGB-300
TUMOUR UPTAKE
title_short Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer
title_full Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer
title_fullStr Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer
title_full_unstemmed Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer
title_sort Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer
dc.creator.none.fl_str_mv Sarduy, M. R.
García, I.
Coca, M. A.
Perera, A.
Torres, L. A.
Valenzuela, C. M.
Baladrón, I.
Solares, M.
Reyes, V.
Hernández, I.
Perera, Y.
Martínez, Y. M.
Molina, L.
González, Y. M.
Ancízar, J. A.
Prats, A.
González, L.
Casacó, C. A.
Acevedo, B. E.
López Saura, P. A.
Alonso, Daniel Fernando
Gómez, R.
Perea Rodríguez, S. E.
author Sarduy, M. R.
author_facet Sarduy, M. R.
García, I.
Coca, M. A.
Perera, A.
Torres, L. A.
Valenzuela, C. M.
Baladrón, I.
Solares, M.
Reyes, V.
Hernández, I.
Perera, Y.
Martínez, Y. M.
Molina, L.
González, Y. M.
Ancízar, J. A.
Prats, A.
González, L.
Casacó, C. A.
Acevedo, B. E.
López Saura, P. A.
Alonso, Daniel Fernando
Gómez, R.
Perea Rodríguez, S. E.
author_role author
author2 García, I.
Coca, M. A.
Perera, A.
Torres, L. A.
Valenzuela, C. M.
Baladrón, I.
Solares, M.
Reyes, V.
Hernández, I.
Perera, Y.
Martínez, Y. M.
Molina, L.
González, Y. M.
Ancízar, J. A.
Prats, A.
González, L.
Casacó, C. A.
Acevedo, B. E.
López Saura, P. A.
Alonso, Daniel Fernando
Gómez, R.
Perea Rodríguez, S. E.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv B23/NUCLEOPHOSMIN
CERVICAL CANCER
CIGB-300
TUMOUR UPTAKE
topic B23/NUCLEOPHOSMIN
CERVICAL CANCER
CIGB-300
TUMOUR UPTAKE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background:We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose.Methods:Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using 99 Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry.Results:Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1±8.9 vs 31.3±12.9 mg (P=0.01). Both, AUC 24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P<0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P=0.03) in tumour specimens.Conclusion:Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.
Fil: Sarduy, M. R.. Medical-surgical Research Center; Cuba
Fil: García, I.. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Coca, M. A.. Clinical Investigation Center; Cuba
Fil: Perera, A.. Clinical Investigation Center; Cuba
Fil: Torres, L. A.. Clinical Investigation Center; Cuba
Fil: Valenzuela, C. M.. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Baladrón, I.. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Solares, M.. Hospital Materno Ramón González Coro; Cuba
Fil: Reyes, V.. Center For Genetic Engineering And Biotechnology Havana; Cuba
Fil: Hernández, I.. Isotope Center; Cuba
Fil: Perera, Y.. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Martínez, Y. M.. Medical-surgical Research Center; Cuba
Fil: Molina, L.. Medical-surgical Research Center; Cuba
Fil: González, Y. M.. Medical-surgical Research Center; Cuba
Fil: Ancízar, J. A.. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Prats, A.. Clinical Investigation Center; Cuba
Fil: González, L.. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Casacó, C. A.. Clinical Investigation Center; Cuba
Fil: Acevedo, B. E.. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: López Saura, P. A.. Centro de Ingeniería Genética y Biotecnología; Cuba
Fil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes; Argentina
Fil: Gómez, R.. Elea Laboratories; Argentina
Fil: Perea Rodríguez, S. E.. Center For Genetic Engineering And Biotechnology Havana; Cuba. Centro de Ingeniería Genética y Biotecnología; Cuba
description Background:We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose.Methods:Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using 99 Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry.Results:Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1±8.9 vs 31.3±12.9 mg (P=0.01). Both, AUC 24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P<0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P=0.03) in tumour specimens.Conclusion:Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.
publishDate 2015
dc.date.none.fl_str_mv 2015-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/96176
Sarduy, M. R.; García, I.; Coca, M. A.; Perera, A.; Torres, L. A.; et al.; Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer; Nature Publishing Group; British Journal Of Cancer; 112; 10; 5-2015; 1636-1643
0007-0920
CONICET Digital
CONICET
url http://hdl.handle.net/11336/96176
identifier_str_mv Sarduy, M. R.; García, I.; Coca, M. A.; Perera, A.; Torres, L. A.; et al.; Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer; Nature Publishing Group; British Journal Of Cancer; 112; 10; 5-2015; 1636-1643
0007-0920
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/bjc2015137
info:eu-repo/semantics/altIdentifier/doi/10.1038/bjc.2015.137
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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