Targeting of T/Tn antigens with a plant lectin to kill human leukemia cells by photochemotherapy.

Photochemotherapy is used both for solid tumors and in extracorporeal treatment of various hematologic disorders. Nevertheless, its development in oncology remains limited, because of the low selectivity of photosensitizers (PS) towards human tumor cells. To enhance PS efficiency, we recently covale...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Guillaume Poiroux, Marguerite Pitié, Raphaël Culerrier, Elodie Lafont, Bruno Ségui, Els J M Van Damme, Willy J Peumans, Jean Bernadou, Thierry Levade, Pierre Rougé, Annick Barre, Hervé Benoist
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2011
Materias:
R
Q
Acceso en línea:https://doaj.org/article/a8620ab1c7fd4b5fb175c50679e15cb8
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:a8620ab1c7fd4b5fb175c50679e15cb8
record_format dspace
spelling oai:doaj.org-article:a8620ab1c7fd4b5fb175c50679e15cb82021-11-18T06:47:49ZTargeting of T/Tn antigens with a plant lectin to kill human leukemia cells by photochemotherapy.1932-620310.1371/journal.pone.0023315https://doaj.org/article/a8620ab1c7fd4b5fb175c50679e15cb82011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21858067/?tool=EBIhttps://doaj.org/toc/1932-6203Photochemotherapy is used both for solid tumors and in extracorporeal treatment of various hematologic disorders. Nevertheless, its development in oncology remains limited, because of the low selectivity of photosensitizers (PS) towards human tumor cells. To enhance PS efficiency, we recently covalently linked a porphyrin (TrMPyP) to a plant lectin (Morniga G), known to recognize with high affinity tumor-associated T and Tn antigens. The conjugation allowed a quick uptake of PS by Tn-positive Jurkat leukemia cells and efficient PS-induced phototoxicity. The present study was performed: (i) to evaluate the targeting potential of the conjugate towards tumor and normal cells and its phototoxicity on various leukemia cells, (ii) to investigate the mechanism of conjugate-mediated cell death. The conjugate: (i) strongly increased (×1000) the PS phototoxicity towards leukemic Jurkat T cells through an O-glycan-dependent process; (ii) specifically purged tumor cells from a 1∶1 mixture of Jurkat leukemia (Tn-positive) and healthy (Tn-negative) lymphocytes, preserving the activation potential of healthy lymphocytes; (iii) was effective against various leukemic cell lines with distinct phenotypes, as well as fresh human primary acute and chronic lymphoid leukemia cells; (iv) induced mostly a caspase-independent cell death, which might be an advantage as tumor cells often resist caspase-dependent cell death. Altogether, the present observations suggest that conjugation with plant lectins can allow targeting of photosensitizers towards aberrant glycosylation of tumor cells, e.g. to purge leukemia cells from blood and to preserve the normal leukocytes in extracorporeal photochemotherapy.Guillaume PoirouxMarguerite PitiéRaphaël CulerrierElodie LafontBruno SéguiEls J M Van DammeWilly J PeumansJean BernadouThierry LevadePierre RougéAnnick BarreHervé BenoistPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 8, p e23315 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Guillaume Poiroux
Marguerite Pitié
Raphaël Culerrier
Elodie Lafont
Bruno Ségui
Els J M Van Damme
Willy J Peumans
Jean Bernadou
Thierry Levade
Pierre Rougé
Annick Barre
Hervé Benoist
Targeting of T/Tn antigens with a plant lectin to kill human leukemia cells by photochemotherapy.
description Photochemotherapy is used both for solid tumors and in extracorporeal treatment of various hematologic disorders. Nevertheless, its development in oncology remains limited, because of the low selectivity of photosensitizers (PS) towards human tumor cells. To enhance PS efficiency, we recently covalently linked a porphyrin (TrMPyP) to a plant lectin (Morniga G), known to recognize with high affinity tumor-associated T and Tn antigens. The conjugation allowed a quick uptake of PS by Tn-positive Jurkat leukemia cells and efficient PS-induced phototoxicity. The present study was performed: (i) to evaluate the targeting potential of the conjugate towards tumor and normal cells and its phototoxicity on various leukemia cells, (ii) to investigate the mechanism of conjugate-mediated cell death. The conjugate: (i) strongly increased (×1000) the PS phototoxicity towards leukemic Jurkat T cells through an O-glycan-dependent process; (ii) specifically purged tumor cells from a 1∶1 mixture of Jurkat leukemia (Tn-positive) and healthy (Tn-negative) lymphocytes, preserving the activation potential of healthy lymphocytes; (iii) was effective against various leukemic cell lines with distinct phenotypes, as well as fresh human primary acute and chronic lymphoid leukemia cells; (iv) induced mostly a caspase-independent cell death, which might be an advantage as tumor cells often resist caspase-dependent cell death. Altogether, the present observations suggest that conjugation with plant lectins can allow targeting of photosensitizers towards aberrant glycosylation of tumor cells, e.g. to purge leukemia cells from blood and to preserve the normal leukocytes in extracorporeal photochemotherapy.
format article
author Guillaume Poiroux
Marguerite Pitié
Raphaël Culerrier
Elodie Lafont
Bruno Ségui
Els J M Van Damme
Willy J Peumans
Jean Bernadou
Thierry Levade
Pierre Rougé
Annick Barre
Hervé Benoist
author_facet Guillaume Poiroux
Marguerite Pitié
Raphaël Culerrier
Elodie Lafont
Bruno Ségui
Els J M Van Damme
Willy J Peumans
Jean Bernadou
Thierry Levade
Pierre Rougé
Annick Barre
Hervé Benoist
author_sort Guillaume Poiroux
title Targeting of T/Tn antigens with a plant lectin to kill human leukemia cells by photochemotherapy.
title_short Targeting of T/Tn antigens with a plant lectin to kill human leukemia cells by photochemotherapy.
title_full Targeting of T/Tn antigens with a plant lectin to kill human leukemia cells by photochemotherapy.
title_fullStr Targeting of T/Tn antigens with a plant lectin to kill human leukemia cells by photochemotherapy.
title_full_unstemmed Targeting of T/Tn antigens with a plant lectin to kill human leukemia cells by photochemotherapy.
title_sort targeting of t/tn antigens with a plant lectin to kill human leukemia cells by photochemotherapy.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/a8620ab1c7fd4b5fb175c50679e15cb8
work_keys_str_mv AT guillaumepoiroux targetingofttnantigenswithaplantlectintokillhumanleukemiacellsbyphotochemotherapy
AT margueritepitie targetingofttnantigenswithaplantlectintokillhumanleukemiacellsbyphotochemotherapy
AT raphaelculerrier targetingofttnantigenswithaplantlectintokillhumanleukemiacellsbyphotochemotherapy
AT elodielafont targetingofttnantigenswithaplantlectintokillhumanleukemiacellsbyphotochemotherapy
AT brunosegui targetingofttnantigenswithaplantlectintokillhumanleukemiacellsbyphotochemotherapy
AT elsjmvandamme targetingofttnantigenswithaplantlectintokillhumanleukemiacellsbyphotochemotherapy
AT willyjpeumans targetingofttnantigenswithaplantlectintokillhumanleukemiacellsbyphotochemotherapy
AT jeanbernadou targetingofttnantigenswithaplantlectintokillhumanleukemiacellsbyphotochemotherapy
AT thierrylevade targetingofttnantigenswithaplantlectintokillhumanleukemiacellsbyphotochemotherapy
AT pierrerouge targetingofttnantigenswithaplantlectintokillhumanleukemiacellsbyphotochemotherapy
AT annickbarre targetingofttnantigenswithaplantlectintokillhumanleukemiacellsbyphotochemotherapy
AT hervebenoist targetingofttnantigenswithaplantlectintokillhumanleukemiacellsbyphotochemotherapy
_version_ 1718424372607188992