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

(2011) PLOS ONE. 6(8).
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Center for nano- and biophotonics (NB-Photonics)
Abstract
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 (x1000) 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.
Keywords
OXIDATIVE STRESS, PHOTODYNAMIC THERAPY, LYMPHOCYTIC-LEUKEMIA, HUMAN-COLON-CANCER, GROWTH-FACTOR RECEPTOR, FLUORESCENT-PROBES, ANTIOXIDANT STATUS, INDUCED APOPTOSIS, SIALOSYL-TN, DEATH

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Citation

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Chicago
Poiroux, Guillaume, Marguerite Pitié, Raphaël Culerrier, Elodie Lafont, Bruno Ségui, Els Van Damme, Willy J Peumans, et al. 2011. “Targeting of T/Tn Antigens with a Plant Lectin to Kill Human Leukemia Cells by Photochemotherapy.” Plos One 6 (8).
APA
Poiroux, G., Pitié, M., Culerrier, R., Lafont, E., Ségui, B., Van Damme, E., Peumans, W. J., et al. (2011). Targeting of T/Tn antigens with a plant lectin to kill human leukemia cells by photochemotherapy. PLOS ONE, 6(8).
Vancouver
1.
Poiroux G, Pitié M, Culerrier R, Lafont E, Ségui B, Van Damme E, et al. Targeting of T/Tn antigens with a plant lectin to kill human leukemia cells by photochemotherapy. PLOS ONE. 2011;6(8).
MLA
Poiroux, Guillaume, Marguerite Pitié, Raphaël Culerrier, et al. “Targeting of T/Tn Antigens with a Plant Lectin to Kill Human Leukemia Cells by Photochemotherapy.” PLOS ONE 6.8 (2011): n. pag. Print.
@article{2140399,
  abstract     = {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 (x1000) 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.},
  articleno    = {e23315},
  author       = {Poiroux, Guillaume and Piti{\'e}, Marguerite and Culerrier, Rapha{\"e}l and Lafont, Elodie and S{\'e}gui, Bruno and Van Damme, Els and Peumans, Willy J and Bernadou, Jean and Levade, Thierry and Roug{\'e}, Pierre and Barre, Annick and Benoist, Herv{\'e}},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keyword      = {OXIDATIVE STRESS,PHOTODYNAMIC THERAPY,LYMPHOCYTIC-LEUKEMIA,HUMAN-COLON-CANCER,GROWTH-FACTOR RECEPTOR,FLUORESCENT-PROBES,ANTIOXIDANT STATUS,INDUCED APOPTOSIS,SIALOSYL-TN,DEATH},
  language     = {eng},
  number       = {8},
  pages        = {11},
  title        = {Targeting of T/Tn antigens with a plant lectin to kill human leukemia cells by photochemotherapy},
  url          = {http://dx.doi.org/10.1371/journal.pone.0023315},
  volume       = {6},
  year         = {2011},
}

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