Publicação
Antibodies for the treatment of brain metastases, a dream or a reality?
| Resumo: | The incidence of brain metastases (BM) in cancer patients is increasing. After diagnosis, overall survival (OS) is poor, elicited by the lack of an effective treatment. Monoclonal antibody (mAb)-based therapy has achieved remarkable success in treating both hematologic and non-central-nervous system (CNS) tumors due to their inherent targeting specificity. However, the use of mAbs in the treatment of CNS tumors is restricted by the blood-brain barrier (BBB) that hinders the delivery of either small-molecules drugs (sMDs) or therapeutic proteins (TPs). To overcome this limitation, active research is focused on the development of strategies to deliver TPs and increase their concentration in the brain. Yet, their molecular weight and hydrophilic nature turn this task into a challenge. The use of BBB peptide shuttles is an elegant strategy. They explore either receptor-mediated transcytosis (RMT) or adsorptive-mediated transcytosis (AMT) to cross the BBB. The latter is preferable since it avoids enzymatic degradation, receptor saturation, and competition with natural receptor substrates, which reduces adverse events. Therefore, the combination of mAbs properties (e.g., selectivity and long half-life) with BBB peptide shuttles (e.g., BBB translocation and delivery into the brain) turns the therapeutic conjugate in a valid approach to safely overcome the BBB and efficiently eliminate metastatic brain cells. |
|---|---|
| Autores principais: | Cavaco, Marco |
| Outros Autores: | Gaspar, Diana; Castanho, Miguel A. R. B.; Neves, Vera |
| Assunto: | Adsorptive-mediated transcytosis Antibody fragments Blood–brain barrier Brain metastases Monoclonal antibodies Peptide shuttles |
| Ano: | 2020 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| _version_ | 1866809602290483200 |
|---|---|
| author | Cavaco, Marco |
| author2 | Gaspar, Diana Castanho, Miguel A. R. B. Neves, Vera |
| author2_role | author author author |
| author_facet | Cavaco, Marco Gaspar, Diana Castanho, Miguel A. R. B. Neves, Vera |
| author_role | author |
| contributor_name_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Cavaco, Marco\",\"Person.identifier.orcid\":\"0000-0002-0938-9038\"},{\"Person.name\":\"Gaspar, Diana\",\"Person.identifier.orcid\":\"0000-0002-9602-567X\"},{\"Person.name\":\"Castanho, Miguel A. R. B.\",\"Person.identifier.orcid\":\"0000-0001-7891-7562\"},{\"Person.name\":\"Neves, Vera\",\"Person.identifier.orcid\":\"0000-0002-2989-7208\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| datacite.creators.creator.creatorName.fl_str_mv | Cavaco, Marco Gaspar, Diana Castanho, Miguel A. R. B. Neves, Vera |
| datacite.date.Accepted.fl_str_mv | 2020-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2021-09-21T15:59:56Z |
| datacite.date.embargoed.fl_str_mv | 2021-09-21T15:59:56Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Adsorptive-mediated transcytosis Antibody fragments Blood–brain barrier Brain metastases Monoclonal antibodies Peptide shuttles |
| datacite.titles.title.fl_str_mv | Antibodies for the treatment of brain metastases, a dream or a reality? |
| dc.contributor.none.fl_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| dc.creator.none.fl_str_mv | Cavaco, Marco Gaspar, Diana Castanho, Miguel A. R. B. Neves, Vera |
| dc.date.Accepted.fl_str_mv | 2020-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2021-09-21T15:59:56Z |
| dc.date.embargoed.fl_str_mv | 2021-09-21T15:59:56Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10451/49569 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | MDPI |
| dc.rights.cclincense.fl_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Adsorptive-mediated transcytosis Antibody fragments Blood–brain barrier Brain metastases Monoclonal antibodies Peptide shuttles |
| dc.title.fl_str_mv | Antibodies for the treatment of brain metastases, a dream or a reality? |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | The incidence of brain metastases (BM) in cancer patients is increasing. After diagnosis, overall survival (OS) is poor, elicited by the lack of an effective treatment. Monoclonal antibody (mAb)-based therapy has achieved remarkable success in treating both hematologic and non-central-nervous system (CNS) tumors due to their inherent targeting specificity. However, the use of mAbs in the treatment of CNS tumors is restricted by the blood-brain barrier (BBB) that hinders the delivery of either small-molecules drugs (sMDs) or therapeutic proteins (TPs). To overcome this limitation, active research is focused on the development of strategies to deliver TPs and increase their concentration in the brain. Yet, their molecular weight and hydrophilic nature turn this task into a challenge. The use of BBB peptide shuttles is an elegant strategy. They explore either receptor-mediated transcytosis (RMT) or adsorptive-mediated transcytosis (AMT) to cross the BBB. The latter is preferable since it avoids enzymatic degradation, receptor saturation, and competition with natural receptor substrates, which reduces adverse events. Therefore, the combination of mAbs properties (e.g., selectivity and long half-life) with BBB peptide shuttles (e.g., BBB translocation and delivery into the brain) turns the therapeutic conjugate in a valid approach to safely overcome the BBB and efficiently eliminate metastatic brain cells. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorio.ulisboa.pt/bitstreams/7e690284-9149-4337-9443-fce78bbc5f56/download |
| id | ul_ea08aacdafcddf35e151c8efddaaa784 |
| identifier.url.fl_str_mv | http://hdl.handle.net/10451/49569 |
| instacron_str | ul |
| institution | Universidade de Lisboa |
| instname_str | Universidade de Lisboa |
| language | eng |
| network_acronym_str | ul |
| network_name_str | Repositório da Universidade de Lisboa |
| oai_identifier_str | oai:repositorio.ulisboa.pt:10451/49569 |
| organization_str_mv | urn:organizationAcronym:ul |
| person_str_mv | Cavaco, Marco Cavaco, Marco https://www.ciencia-id.pt/1412-63B8-7494 1412-63B8-7494 http://orcid.org/0000-0002-0938-9038 0000-0002-0938-9038 Gaspar, Diana Gaspar, Diana http://orcid.org/0000-0002-9602-567X 0000-0002-9602-567X Castanho, Miguel A. R. B. Castanho, Miguel A. R. B. http://orcid.org/0000-0001-7891-7562 0000-0001-7891-7562 Neves, Vera Neves, Vera https://www.ciencia-id.pt/671C-1860-A160 671C-1860-A160 http://orcid.org/0000-0002-2989-7208 0000-0002-2989-7208 |
| publishDate | 2020 |
| publisher.none.fl_str_mv | MDPI |
| reponame_str | Repositório da Universidade de Lisboa |
| repository_id_str | urn:repositoryAcronym:ul |
| service_str_mv | urn:repositoryAcronym:ul |
| spelling | engMDPIpt_PTThe incidence of brain metastases (BM) in cancer patients is increasing. After diagnosis, overall survival (OS) is poor, elicited by the lack of an effective treatment. Monoclonal antibody (mAb)-based therapy has achieved remarkable success in treating both hematologic and non-central-nervous system (CNS) tumors due to their inherent targeting specificity. However, the use of mAbs in the treatment of CNS tumors is restricted by the blood-brain barrier (BBB) that hinders the delivery of either small-molecules drugs (sMDs) or therapeutic proteins (TPs). To overcome this limitation, active research is focused on the development of strategies to deliver TPs and increase their concentration in the brain. Yet, their molecular weight and hydrophilic nature turn this task into a challenge. The use of BBB peptide shuttles is an elegant strategy. They explore either receptor-mediated transcytosis (RMT) or adsorptive-mediated transcytosis (AMT) to cross the BBB. The latter is preferable since it avoids enzymatic degradation, receptor saturation, and competition with natural receptor substrates, which reduces adverse events. Therefore, the combination of mAbs properties (e.g., selectivity and long half-life) with BBB peptide shuttles (e.g., BBB translocation and delivery into the brain) turns the therapeutic conjugate in a valid approach to safely overcome the BBB and efficiently eliminate metastatic brain cells.application/pdfpt_PTAntibodies for the treatment of brain metastases, a dream or a reality?PersonalCavaco, MarcoDSpacehttp://dspace.org/items/ce7bbed1-4210-464f-93ac-f270ca7d2140DSpacehttp://dspace.org/items/ce7bbed1-4210-464f-93ac-f270ca7d2140CavacoMarcoCiência IDhttps://www.ciencia-id.pt1412-63B8-7494ORCIDhttp://orcid.org0000-0002-0938-9038PersonalGaspar, DianaDSpacehttp://dspace.org/items/9fe9e286-d492-4b04-b6ba-5b214f661b7fDSpacehttp://dspace.org/items/9fe9e286-d492-4b04-b6ba-5b214f661b7fGasparDianaORCIDhttp://orcid.org0000-0002-9602-567XResearcher IDhttps://www.researcherid.comM-9562-2015Scopus Author IDhttps://www.scopus.com55180303000PersonalCastanho, Miguel A. R. B.DSpacehttp://dspace.org/items/f5e46f85-fabf-450a-9ee2-1c7b59410892DSpacehttp://dspace.org/items/f5e46f85-fabf-450a-9ee2-1c7b59410892CastanhoMiguelORCIDhttp://orcid.org0000-0001-7891-7562Scopus Author IDhttps://www.scopus.com56605575600PersonalNeves, VeraDSpacehttp://dspace.org/items/f62bb731-3f4d-4eaf-bc6b-dd379f6c2327DSpacehttp://dspace.org/items/f62bb731-3f4d-4eaf-bc6b-dd379f6c2327NevesVeraCiência IDhttps://www.ciencia-id.pt671C-1860-A160ORCIDhttp://orcid.org0000-0002-2989-7208Researcher IDhttps://www.researcherid.comO-2176-2018Scopus Author IDhttps://www.scopus.com26537945300HostingInstitutionOrganizationalRepositório Científico de Acesso Aberto da ULisboae-mailmailto:repositorio@reitoria.ulisboa.ptrepositorio@reitoria.ulisboa.ptDOIIsPartOf10.3390/pharmaceutics120100622021-09-21T15:59:56Z20202020-01-01T00:00:00ZHandlehttp://hdl.handle.net/10451/49569http://purl.org/coar/access_right/c_abf2open accessAdsorptive-mediated transcytosisAntibody fragmentsBlood–brain barrierBrain metastasesMonoclonal antibodiesPeptide shuttles3102969 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal article2020http://creativecommons.org/licenses/by/4.0/http://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorio.ulisboa.pt/bitstreams/7e690284-9149-4337-9443-fce78bbc5f56/downloadPharmaceutics121 |
| spellingShingle | Antibodies for the treatment of brain metastases, a dream or a reality? Cavaco, Marco Adsorptive-mediated transcytosis Antibody fragments Blood–brain barrier Brain metastases Monoclonal antibodies Peptide shuttles |
| status | SINGLETON |
| subject.fl_str_mv | Adsorptive-mediated transcytosis Antibody fragments Blood–brain barrier Brain metastases Monoclonal antibodies Peptide shuttles |
| title | Antibodies for the treatment of brain metastases, a dream or a reality? |
| title_full | Antibodies for the treatment of brain metastases, a dream or a reality? |
| title_fullStr | Antibodies for the treatment of brain metastases, a dream or a reality? |
| title_full_unstemmed | Antibodies for the treatment of brain metastases, a dream or a reality? |
| title_short | Antibodies for the treatment of brain metastases, a dream or a reality? |
| title_sort | Antibodies for the treatment of brain metastases, a dream or a reality? |
| topic | Adsorptive-mediated transcytosis Antibody fragments Blood–brain barrier Brain metastases Monoclonal antibodies Peptide shuttles |
| topic_facet | Adsorptive-mediated transcytosis Antibody fragments Blood–brain barrier Brain metastases Monoclonal antibodies Peptide shuttles |
| url | http://hdl.handle.net/10451/49569 |
| visible | 1 |