An Antibody-based Multifaceted Approach Targeting the Human Transferrin Receptor for the Treatment of B-cell Malignancies

Autores
Daniels, Tracy R.; Ortiz Sanchez, Elizabeth; Luria Pérez, Rosendo; Quintero, Rafaela; Helguera, Gustavo Fernando; Bonavida, Benjamin; Martinez Maza, Otoniel; Penichet, Manuel L.
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We previously developed an antibody-avidin fusion protein (ch128.1Av) targeting the human transferrin receptor 1 (TfR1, also known as CD71), which demonstrates direct in vitro cytotoxicity against malignant hematopoietic cells. This cytotoxicity is attributed to its ability to decrease the level of TfR1 leading to lethal iron deprivation. We now report that ch128.1Av shows the ability to bind the Fc γ receptors and the complement component C1q, suggesting that it is capable of eliciting Fcmediated effector functions such as antibody-dependent cellmediated cytotoxicity and complement-mediated cytotoxicity. In addition, in 2 disseminated multiple myeloma xenograft mouse models, we show that a single dose of ch128.1Av results in significant antitumor activity, including long-term survival. It is interesting to note that the parental antibody without avidin (ch128.1) also shows remarkable in vivo anticancer activity despite its limited in vitro cytotoxicity. Finally, we demonstrate that ch128.1Av is not toxic to pluripotent hematopoietic progenitor cells using the long-term cell-initiating culture assay suggesting that these important progenitors would be preserved in different therapeutic approaches, including the in vitro purging of cancer cells for autologous transplantation and in vivo passive immunotherapy. Our results suggest that ch128.1Av and ch128.1 may be effective in the therapy of human multiple myeloma and potentially other hematopoietic malignancies.
Fil: Daniels, Tracy R.. David Geffen School of Medicine; Estados Unidos
Fil: Ortiz Sanchez, Elizabeth. David Geffen School of Medicine; Estados Unidos. Instituto Nacional de Cancerología; México
Fil: Luria Pérez, Rosendo. David Geffen School of Medicine; Estados Unidos. Hospital Infantil de México "Federico Gómez"; México
Fil: Quintero, Rafaela. David Geffen School of Medicine; Estados Unidos
Fil: Helguera, Gustavo Fernando. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. David Geffen School of Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Bonavida, Benjamin. University of California; Estados Unidos
Fil: Martinez Maza, Otoniel. University of California; Estados Unidos
Fil: Penichet, Manuel L.. David Geffen School of Medicine; Estados Unidos. University of California; Estados Unidos
Materia
Transferrin Receptor
Cd71
Antibody Fusion Protein
Cancer
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:11336/12925
Acceder
id CONICETDig_120bf6e0e1510126413848b754635e91
oai_identifier_str oai:ri.conicet.gov.ar:11336/12925
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling An Antibody-based Multifaceted Approach Targeting the Human Transferrin Receptor for the Treatment of B-cell MalignanciesDaniels, Tracy R.Ortiz Sanchez, ElizabethLuria Pérez, RosendoQuintero, RafaelaHelguera, Gustavo FernandoBonavida, BenjaminMartinez Maza, OtonielPenichet, Manuel L.Transferrin ReceptorCd71Antibody Fusion ProteinCancerhttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3We previously developed an antibody-avidin fusion protein (ch128.1Av) targeting the human transferrin receptor 1 (TfR1, also known as CD71), which demonstrates direct in vitro cytotoxicity against malignant hematopoietic cells. This cytotoxicity is attributed to its ability to decrease the level of TfR1 leading to lethal iron deprivation. We now report that ch128.1Av shows the ability to bind the Fc γ receptors and the complement component C1q, suggesting that it is capable of eliciting Fcmediated effector functions such as antibody-dependent cellmediated cytotoxicity and complement-mediated cytotoxicity. In addition, in 2 disseminated multiple myeloma xenograft mouse models, we show that a single dose of ch128.1Av results in significant antitumor activity, including long-term survival. It is interesting to note that the parental antibody without avidin (ch128.1) also shows remarkable in vivo anticancer activity despite its limited in vitro cytotoxicity. Finally, we demonstrate that ch128.1Av is not toxic to pluripotent hematopoietic progenitor cells using the long-term cell-initiating culture assay suggesting that these important progenitors would be preserved in different therapeutic approaches, including the in vitro purging of cancer cells for autologous transplantation and in vivo passive immunotherapy. Our results suggest that ch128.1Av and ch128.1 may be effective in the therapy of human multiple myeloma and potentially other hematopoietic malignancies.Fil: Daniels, Tracy R.. David Geffen School of Medicine; Estados UnidosFil: Ortiz Sanchez, Elizabeth. David Geffen School of Medicine; Estados Unidos. Instituto Nacional de Cancerología; MéxicoFil: Luria Pérez, Rosendo. David Geffen School of Medicine; Estados Unidos. Hospital Infantil de México "Federico Gómez"; MéxicoFil: Quintero, Rafaela. David Geffen School of Medicine; Estados UnidosFil: Helguera, Gustavo Fernando. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. David Geffen School of Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Bonavida, Benjamin. University of California; Estados UnidosFil: Martinez Maza, Otoniel. University of California; Estados UnidosFil: Penichet, Manuel L.. David Geffen School of Medicine; Estados Unidos. University of California; Estados UnidosLippincott Williams2011-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/12925Daniels, Tracy R.; Ortiz Sanchez, Elizabeth; Luria Pérez, Rosendo; Quintero, Rafaela; Helguera, Gustavo Fernando; et al.; An Antibody-based Multifaceted Approach Targeting the Human Transferrin Receptor for the Treatment of B-cell Malignancies; Lippincott Williams; Journal Of Immunotherapy; 34; 6; 11-2011; 500-5081524-9557enginfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717268/info:eu-repo/semantics/altIdentifier/url/http://journals.lww.com/immunotherapy-journal/pages/articleviewer.aspx?year=2011&issue=07000&article=00004&type=abstractinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:42:50Zoai:ri.conicet.gov.ar:11336/12925instacron: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:34982025-09-29 09:42:50.317CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv An Antibody-based Multifaceted Approach Targeting the Human Transferrin Receptor for the Treatment of B-cell Malignancies
title An Antibody-based Multifaceted Approach Targeting the Human Transferrin Receptor for the Treatment of B-cell Malignancies
spellingShingle An Antibody-based Multifaceted Approach Targeting the Human Transferrin Receptor for the Treatment of B-cell Malignancies
Daniels, Tracy R.
Transferrin Receptor
Cd71
Antibody Fusion Protein
Cancer
title_short An Antibody-based Multifaceted Approach Targeting the Human Transferrin Receptor for the Treatment of B-cell Malignancies
title_full An Antibody-based Multifaceted Approach Targeting the Human Transferrin Receptor for the Treatment of B-cell Malignancies
title_fullStr An Antibody-based Multifaceted Approach Targeting the Human Transferrin Receptor for the Treatment of B-cell Malignancies
title_full_unstemmed An Antibody-based Multifaceted Approach Targeting the Human Transferrin Receptor for the Treatment of B-cell Malignancies
title_sort An Antibody-based Multifaceted Approach Targeting the Human Transferrin Receptor for the Treatment of B-cell Malignancies
dc.creator.none.fl_str_mv Daniels, Tracy R.
Ortiz Sanchez, Elizabeth
Luria Pérez, Rosendo
Quintero, Rafaela
Helguera, Gustavo Fernando
Bonavida, Benjamin
Martinez Maza, Otoniel
Penichet, Manuel L.
author Daniels, Tracy R.
author_facet Daniels, Tracy R.
Ortiz Sanchez, Elizabeth
Luria Pérez, Rosendo
Quintero, Rafaela
Helguera, Gustavo Fernando
Bonavida, Benjamin
Martinez Maza, Otoniel
Penichet, Manuel L.
author_role author
author2 Ortiz Sanchez, Elizabeth
Luria Pérez, Rosendo
Quintero, Rafaela
Helguera, Gustavo Fernando
Bonavida, Benjamin
Martinez Maza, Otoniel
Penichet, Manuel L.
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Transferrin Receptor
Cd71
Antibody Fusion Protein
Cancer
topic Transferrin Receptor
Cd71
Antibody Fusion Protein
Cancer
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv We previously developed an antibody-avidin fusion protein (ch128.1Av) targeting the human transferrin receptor 1 (TfR1, also known as CD71), which demonstrates direct in vitro cytotoxicity against malignant hematopoietic cells. This cytotoxicity is attributed to its ability to decrease the level of TfR1 leading to lethal iron deprivation. We now report that ch128.1Av shows the ability to bind the Fc γ receptors and the complement component C1q, suggesting that it is capable of eliciting Fcmediated effector functions such as antibody-dependent cellmediated cytotoxicity and complement-mediated cytotoxicity. In addition, in 2 disseminated multiple myeloma xenograft mouse models, we show that a single dose of ch128.1Av results in significant antitumor activity, including long-term survival. It is interesting to note that the parental antibody without avidin (ch128.1) also shows remarkable in vivo anticancer activity despite its limited in vitro cytotoxicity. Finally, we demonstrate that ch128.1Av is not toxic to pluripotent hematopoietic progenitor cells using the long-term cell-initiating culture assay suggesting that these important progenitors would be preserved in different therapeutic approaches, including the in vitro purging of cancer cells for autologous transplantation and in vivo passive immunotherapy. Our results suggest that ch128.1Av and ch128.1 may be effective in the therapy of human multiple myeloma and potentially other hematopoietic malignancies.
Fil: Daniels, Tracy R.. David Geffen School of Medicine; Estados Unidos
Fil: Ortiz Sanchez, Elizabeth. David Geffen School of Medicine; Estados Unidos. Instituto Nacional de Cancerología; México
Fil: Luria Pérez, Rosendo. David Geffen School of Medicine; Estados Unidos. Hospital Infantil de México "Federico Gómez"; México
Fil: Quintero, Rafaela. David Geffen School of Medicine; Estados Unidos
Fil: Helguera, Gustavo Fernando. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. David Geffen School of Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Bonavida, Benjamin. University of California; Estados Unidos
Fil: Martinez Maza, Otoniel. University of California; Estados Unidos
Fil: Penichet, Manuel L.. David Geffen School of Medicine; Estados Unidos. University of California; Estados Unidos
description We previously developed an antibody-avidin fusion protein (ch128.1Av) targeting the human transferrin receptor 1 (TfR1, also known as CD71), which demonstrates direct in vitro cytotoxicity against malignant hematopoietic cells. This cytotoxicity is attributed to its ability to decrease the level of TfR1 leading to lethal iron deprivation. We now report that ch128.1Av shows the ability to bind the Fc γ receptors and the complement component C1q, suggesting that it is capable of eliciting Fcmediated effector functions such as antibody-dependent cellmediated cytotoxicity and complement-mediated cytotoxicity. In addition, in 2 disseminated multiple myeloma xenograft mouse models, we show that a single dose of ch128.1Av results in significant antitumor activity, including long-term survival. It is interesting to note that the parental antibody without avidin (ch128.1) also shows remarkable in vivo anticancer activity despite its limited in vitro cytotoxicity. Finally, we demonstrate that ch128.1Av is not toxic to pluripotent hematopoietic progenitor cells using the long-term cell-initiating culture assay suggesting that these important progenitors would be preserved in different therapeutic approaches, including the in vitro purging of cancer cells for autologous transplantation and in vivo passive immunotherapy. Our results suggest that ch128.1Av and ch128.1 may be effective in the therapy of human multiple myeloma and potentially other hematopoietic malignancies.
publishDate 2011
dc.date.none.fl_str_mv 2011-11
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/11336/12925
Daniels, Tracy R.; Ortiz Sanchez, Elizabeth; Luria Pérez, Rosendo; Quintero, Rafaela; Helguera, Gustavo Fernando; et al.; An Antibody-based Multifaceted Approach Targeting the Human Transferrin Receptor for the Treatment of B-cell Malignancies; Lippincott Williams; Journal Of Immunotherapy; 34; 6; 11-2011; 500-508
1524-9557
url http://hdl.handle.net/11336/12925
identifier_str_mv Daniels, Tracy R.; Ortiz Sanchez, Elizabeth; Luria Pérez, Rosendo; Quintero, Rafaela; Helguera, Gustavo Fernando; et al.; An Antibody-based Multifaceted Approach Targeting the Human Transferrin Receptor for the Treatment of B-cell Malignancies; Lippincott Williams; Journal Of Immunotherapy; 34; 6; 11-2011; 500-508
1524-9557
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717268/
info:eu-repo/semantics/altIdentifier/url/http://journals.lww.com/immunotherapy-journal/pages/articleviewer.aspx?year=2011&issue=07000&article=00004&type=abstract
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 Lippincott Williams
publisher.none.fl_str_mv Lippincott Williams
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
_version_ 1844613348421795840
score 13.070432

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