Bispecific antibodies targeting tumor-associated antigens and neutralizing complement regulators increase the efficacy of antibody-based immunotherapy in mice

Claudio Tripodo, Paolo Durigutto, Erika Secco, De Maso, Stefania Biffi, Gaiotto, Francesco Tedesco, Chiara Garrovo, Nelly Mezzaroba, Sara Capolla, Paolo Macor, Sblattero, Roberto Marzari, Sonia Zorzet, Valter Gattei

Risultato della ricerca: Article

22 Citazioni (Scopus)

Abstract

The efficacy of antibody-based immunotherapy is due to the activation of apoptosis, the engagement of antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity (CDC). We developed a novel strategy to enhance CDC using bispecific antibodies (bsAbs) that neutralize the C-regulators CD55 and CD59 to enhance C-mediated functions. Two bsAbs (MB20/55 and MB20/59) were designed to recognize CD20 on one side. The other side neutralizes CD55 or CD59. Analysis of CDC revealed that bsAbs could kill 4-25 times more cells than anti-CD20 recombinant antibody in cell lines or cells isolated from patients with chronic lymphocytic leukemia. The pharmacokinetics of the bsAbs was evaluated in a human-SCID model of Burkitt lymphoma. The distribution profile of bsAbs mimics the data obtained by studying the pharmacokinetics of anti-CD20 antibodies, showing a peak in the tumor mass 3-4 days after injection. The treatment with bsAbs completely prevented the development of human/SCID lymphoma. The tumor growth was blocked by the activation of the C cascade and by the recruitment of macrophages, polymorphonuclear and natural killer cells. This strategy can easily be applied to the other anti-tumor C-fixing antibodies currently used in the clinic or tested in preclinical studies using the same vector with the appropriate modifications.
Lingua originaleEnglish
pagine (da-a)406-414
Numero di pagine9
RivistaLeukemia
Volume29
Stato di pubblicazionePublished - 2015

Fingerprint

Bispecific Antibodies
Neoplasm Antigens
Immunotherapy
Antibodies
Pharmacokinetics
Neoplasms
Burkitt Lymphoma
Human Development
B-Cell Chronic Lymphocytic Leukemia
Natural Killer Cells
Anti-Idiotypic Antibodies
Lymphoma
Macrophages
Apoptosis
Cell Line
Injections
Growth

All Science Journal Classification (ASJC) codes

  • Oncology
  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine
  • Medicine(all)

Cita questo

Bispecific antibodies targeting tumor-associated antigens and neutralizing complement regulators increase the efficacy of antibody-based immunotherapy in mice. / Tripodo, Claudio; Durigutto, Paolo; Secco, Erika; De Maso; Biffi, Stefania; Gaiotto; Tedesco, Francesco; Garrovo, Chiara; Mezzaroba, Nelly; Capolla, Sara; Macor, Paolo; Sblattero; Marzari, Roberto; Zorzet, Sonia; Gattei, Valter.

In: Leukemia, Vol. 29, 2015, pag. 406-414.

Risultato della ricerca: Article

Tripodo, C, Durigutto, P, Secco, E, De Maso, Biffi, S, Gaiotto, Tedesco, F, Garrovo, C, Mezzaroba, N, Capolla, S, Macor, P, Sblattero, Marzari, R, Zorzet, S & Gattei, V 2015, 'Bispecific antibodies targeting tumor-associated antigens and neutralizing complement regulators increase the efficacy of antibody-based immunotherapy in mice', Leukemia, vol. 29, pagg. 406-414.
Tripodo, Claudio ; Durigutto, Paolo ; Secco, Erika ; De Maso ; Biffi, Stefania ; Gaiotto ; Tedesco, Francesco ; Garrovo, Chiara ; Mezzaroba, Nelly ; Capolla, Sara ; Macor, Paolo ; Sblattero ; Marzari, Roberto ; Zorzet, Sonia ; Gattei, Valter. / Bispecific antibodies targeting tumor-associated antigens and neutralizing complement regulators increase the efficacy of antibody-based immunotherapy in mice. In: Leukemia. 2015 ; Vol. 29. pagg. 406-414.
@article{78c58170085a4e5fa2ed92371245fe5d,
title = "Bispecific antibodies targeting tumor-associated antigens and neutralizing complement regulators increase the efficacy of antibody-based immunotherapy in mice",
abstract = "The efficacy of antibody-based immunotherapy is due to the activation of apoptosis, the engagement of antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity (CDC). We developed a novel strategy to enhance CDC using bispecific antibodies (bsAbs) that neutralize the C-regulators CD55 and CD59 to enhance C-mediated functions. Two bsAbs (MB20/55 and MB20/59) were designed to recognize CD20 on one side. The other side neutralizes CD55 or CD59. Analysis of CDC revealed that bsAbs could kill 4-25 times more cells than anti-CD20 recombinant antibody in cell lines or cells isolated from patients with chronic lymphocytic leukemia. The pharmacokinetics of the bsAbs was evaluated in a human-SCID model of Burkitt lymphoma. The distribution profile of bsAbs mimics the data obtained by studying the pharmacokinetics of anti-CD20 antibodies, showing a peak in the tumor mass 3-4 days after injection. The treatment with bsAbs completely prevented the development of human/SCID lymphoma. The tumor growth was blocked by the activation of the C cascade and by the recruitment of macrophages, polymorphonuclear and natural killer cells. This strategy can easily be applied to the other anti-tumor C-fixing antibodies currently used in the clinic or tested in preclinical studies using the same vector with the appropriate modifications.",
author = "Claudio Tripodo and Paolo Durigutto and Erika Secco and {De Maso} and Stefania Biffi and Gaiotto and Francesco Tedesco and Chiara Garrovo and Nelly Mezzaroba and Sara Capolla and Paolo Macor and Sblattero and Roberto Marzari and Sonia Zorzet and Valter Gattei",
year = "2015",
language = "English",
volume = "29",
pages = "406--414",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Bispecific antibodies targeting tumor-associated antigens and neutralizing complement regulators increase the efficacy of antibody-based immunotherapy in mice

AU - Tripodo, Claudio

AU - Durigutto, Paolo

AU - Secco, Erika

AU - De Maso, null

AU - Biffi, Stefania

AU - Gaiotto, null

AU - Tedesco, Francesco

AU - Garrovo, Chiara

AU - Mezzaroba, Nelly

AU - Capolla, Sara

AU - Macor, Paolo

AU - Sblattero, null

AU - Marzari, Roberto

AU - Zorzet, Sonia

AU - Gattei, Valter

PY - 2015

Y1 - 2015

N2 - The efficacy of antibody-based immunotherapy is due to the activation of apoptosis, the engagement of antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity (CDC). We developed a novel strategy to enhance CDC using bispecific antibodies (bsAbs) that neutralize the C-regulators CD55 and CD59 to enhance C-mediated functions. Two bsAbs (MB20/55 and MB20/59) were designed to recognize CD20 on one side. The other side neutralizes CD55 or CD59. Analysis of CDC revealed that bsAbs could kill 4-25 times more cells than anti-CD20 recombinant antibody in cell lines or cells isolated from patients with chronic lymphocytic leukemia. The pharmacokinetics of the bsAbs was evaluated in a human-SCID model of Burkitt lymphoma. The distribution profile of bsAbs mimics the data obtained by studying the pharmacokinetics of anti-CD20 antibodies, showing a peak in the tumor mass 3-4 days after injection. The treatment with bsAbs completely prevented the development of human/SCID lymphoma. The tumor growth was blocked by the activation of the C cascade and by the recruitment of macrophages, polymorphonuclear and natural killer cells. This strategy can easily be applied to the other anti-tumor C-fixing antibodies currently used in the clinic or tested in preclinical studies using the same vector with the appropriate modifications.

AB - The efficacy of antibody-based immunotherapy is due to the activation of apoptosis, the engagement of antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity (CDC). We developed a novel strategy to enhance CDC using bispecific antibodies (bsAbs) that neutralize the C-regulators CD55 and CD59 to enhance C-mediated functions. Two bsAbs (MB20/55 and MB20/59) were designed to recognize CD20 on one side. The other side neutralizes CD55 or CD59. Analysis of CDC revealed that bsAbs could kill 4-25 times more cells than anti-CD20 recombinant antibody in cell lines or cells isolated from patients with chronic lymphocytic leukemia. The pharmacokinetics of the bsAbs was evaluated in a human-SCID model of Burkitt lymphoma. The distribution profile of bsAbs mimics the data obtained by studying the pharmacokinetics of anti-CD20 antibodies, showing a peak in the tumor mass 3-4 days after injection. The treatment with bsAbs completely prevented the development of human/SCID lymphoma. The tumor growth was blocked by the activation of the C cascade and by the recruitment of macrophages, polymorphonuclear and natural killer cells. This strategy can easily be applied to the other anti-tumor C-fixing antibodies currently used in the clinic or tested in preclinical studies using the same vector with the appropriate modifications.

UR - http://hdl.handle.net/10447/203496

UR - http://www.nature.com/leu/index.html

M3 - Article

VL - 29

SP - 406

EP - 414

JO - Leukemia

JF - Leukemia

SN - 0887-6924

ER -