Expansion of allogeneic NK cells with efficient antibody-dependent cell cytotoxicity against multiple tumors

Diego Sanchez-Martinez, Nerea Allende-Vega, Stefania Orecchioni, Giovanna Talarico, Amelie Cornillon, Dang Nghiem Vo, Celine Rene, Zhao Yang Lu, Ewelina Krzywinska, Alberto Anel, Eva M. Galvez, Julian Pardo, Bruno Robert, Pierre Martineau, Yosr Hicheri, Francesco Bertolini, Guillaume Cartron, Martin Villalba

Research output: Contribution to journalArticle

Abstract

Monoclonal antibodies (mAbs) have significantly improved the treatment of certain cancers. However, in general mAbs alone have limited therapeutic activity. One of their main mechanisms of action is to induce antibody-dependent cell-mediated cytotoxicity (ADCC), which is mediated by natural killer (NK) cells. Unfortunately, most cancer patients have severe immune dysfunctions affecting NK activity. This can be circumvented by the injection of allogeneic, expanded NK cells, which is safe. Nevertheless, despite their strong cytolytic potential against different tumors, clinical results have been poor. Methods: We combined allogeneic NK cells and mAbs to improve cancer treatment. We generated expanded NK cells (e-NK) with strong in vitro and in vivo ADCC responses against different tumors and using different therapeutic mAbs, namely rituximab, obinutuzumab, daratumumab, cetuximab and trastuzumab. Results: Remarkably, e-NK cells can be stored frozen and, after thawing, armed with mAbs. They mediate ADCC through degranulation-dependent and -independent mechanisms. Furthermore, they overcome certain anti-apoptotic mechanisms found in leukemic cells. Conclusion: We have established a new protocol for activation/expansion of NK cells with high ADCC activity. The use of mAbs in combination with e-NK cells could potentially improve cancer treatment.

Original languageEnglish
Pages (from-to)3856-3869
Number of pages14
JournalTheranostics
Volume8
Issue number14
DOIs
Publication statusPublished - Jan 1 2018

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Antibody-Dependent Cell Cytotoxicity
Natural Killer Cells
Monoclonal Antibodies
Neoplasms
Therapeutics
Injections

Keywords

  • Antibody-dependent cell cytotoxicity (ADCC)
  • Cancer
  • Monoclonal antibodies (mAbs)
  • NK cells

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

Cite this

Expansion of allogeneic NK cells with efficient antibody-dependent cell cytotoxicity against multiple tumors. / Sanchez-Martinez, Diego; Allende-Vega, Nerea; Orecchioni, Stefania; Talarico, Giovanna; Cornillon, Amelie; Vo, Dang Nghiem; Rene, Celine; Lu, Zhao Yang; Krzywinska, Ewelina; Anel, Alberto; Galvez, Eva M.; Pardo, Julian; Robert, Bruno; Martineau, Pierre; Hicheri, Yosr; Bertolini, Francesco; Cartron, Guillaume; Villalba, Martin.

In: Theranostics, Vol. 8, No. 14, 01.01.2018, p. 3856-3869.

Research output: Contribution to journalArticle

Sanchez-Martinez, D, Allende-Vega, N, Orecchioni, S, Talarico, G, Cornillon, A, Vo, DN, Rene, C, Lu, ZY, Krzywinska, E, Anel, A, Galvez, EM, Pardo, J, Robert, B, Martineau, P, Hicheri, Y, Bertolini, F, Cartron, G & Villalba, M 2018, 'Expansion of allogeneic NK cells with efficient antibody-dependent cell cytotoxicity against multiple tumors', Theranostics, vol. 8, no. 14, pp. 3856-3869. https://doi.org/10.7150/thno.25149
Sanchez-Martinez, Diego ; Allende-Vega, Nerea ; Orecchioni, Stefania ; Talarico, Giovanna ; Cornillon, Amelie ; Vo, Dang Nghiem ; Rene, Celine ; Lu, Zhao Yang ; Krzywinska, Ewelina ; Anel, Alberto ; Galvez, Eva M. ; Pardo, Julian ; Robert, Bruno ; Martineau, Pierre ; Hicheri, Yosr ; Bertolini, Francesco ; Cartron, Guillaume ; Villalba, Martin. / Expansion of allogeneic NK cells with efficient antibody-dependent cell cytotoxicity against multiple tumors. In: Theranostics. 2018 ; Vol. 8, No. 14. pp. 3856-3869.
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AU - Allende-Vega, Nerea

AU - Orecchioni, Stefania

AU - Talarico, Giovanna

AU - Cornillon, Amelie

AU - Vo, Dang Nghiem

AU - Rene, Celine

AU - Lu, Zhao Yang

AU - Krzywinska, Ewelina

AU - Anel, Alberto

AU - Galvez, Eva M.

AU - Pardo, Julian

AU - Robert, Bruno

AU - Martineau, Pierre

AU - Hicheri, Yosr

AU - Bertolini, Francesco

AU - Cartron, Guillaume

AU - Villalba, Martin

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N2 - Monoclonal antibodies (mAbs) have significantly improved the treatment of certain cancers. However, in general mAbs alone have limited therapeutic activity. One of their main mechanisms of action is to induce antibody-dependent cell-mediated cytotoxicity (ADCC), which is mediated by natural killer (NK) cells. Unfortunately, most cancer patients have severe immune dysfunctions affecting NK activity. This can be circumvented by the injection of allogeneic, expanded NK cells, which is safe. Nevertheless, despite their strong cytolytic potential against different tumors, clinical results have been poor. Methods: We combined allogeneic NK cells and mAbs to improve cancer treatment. We generated expanded NK cells (e-NK) with strong in vitro and in vivo ADCC responses against different tumors and using different therapeutic mAbs, namely rituximab, obinutuzumab, daratumumab, cetuximab and trastuzumab. Results: Remarkably, e-NK cells can be stored frozen and, after thawing, armed with mAbs. They mediate ADCC through degranulation-dependent and -independent mechanisms. Furthermore, they overcome certain anti-apoptotic mechanisms found in leukemic cells. Conclusion: We have established a new protocol for activation/expansion of NK cells with high ADCC activity. The use of mAbs in combination with e-NK cells could potentially improve cancer treatment.

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